A depressant, or central depressant, is a

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhal ...

that lowers neurotransmission levels, which is to depress or reduce

arousal Arousal is the physiological and psychological state of being awoken or of sense organs stimulated to a point of perception. It involves activation of the ascending reticular activating system (ARAS) in the brain, which mediates wakefulness, th ...

stimulation Stimulation is the encouragement of development or the cause of activity generally. For example, "The press provides stimulation of political discourse." An interesting or fun activity can be described as "stimulating", regardless of its physic ...

, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the level of arousal when taken.

Stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

s or "uppers" increase mental or physical function, hence the opposite drug class of depressants is stimulants, not

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness ...

s. Depressants are widely used throughout the world as prescription medicines and as

illicit substances A controlled substance is generally a drug or chemical whose manufacture, possession and use is regulated by a government, such as illicitly used drugs or prescription medications that are designated by law. Some treaties, notably the Single ...

. Alcohol is a very prominent depressant. Alcohol can be and is more likely to be a large problem among teenagers and young adults. When depressants are used, effects often include ataxia, anxiolysis,

pain relief Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...

, sedation or somnolence, and

cognitive Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought ...

or memory impairment, as well as in some instances,

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and dan ...

, dissociation, muscle relaxation, lowered

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressur ...

heart rate Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and e ...

, respiratory depression, and anticonvulsant effects. Depressants also act to produce

anesthesia Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), a ...

. Cannabis may sometimes be considered a depressant due to one of its components, cannabidiol. The latter is known to treat insomnia, anxiety and muscle spasms similar to other depressive drugs. However,

tetrahydrocannabinol Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC' ...

, another component, may slow brain function to a small degree while reducing reaction to stimuli, it is generally considered to be a stimulant and main psychoactive agent to sometimes cause anxiety,

panic Panic is a sudden sensation of fear, which is so strong as to dominate or prevent reason and logical thinking, replacing it with overwhelming feelings of anxiety and frantic agitation consistent with an animalistic fight-or-flight reac ...

and psychosis instead. Other depressants can include drugs like

Xanax Alprazolam, sold under the brand name Xanax, among others, is a fast-acting, potent tranquilizer of medium duration in the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. It is most commonl ...

(a benzodiazepine) and a number of

opioids Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...

. Gabapentinoids like

gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diab ...

and baclofen are depressants and have anticonvulsant and anxiolytic effects. Most anticonvulsants like Lamotrigine and Phenytoin are depressants. Carbamates ( Felbamate Carisoprodol) are depressants that are similar to barbiturates. Depressants exert their effects through a number of different pharmacological mechanisms, the most prominent of which include facilitation of GABA, and inhibition of glutamatergic or

monoaminergic Monoaminergic means "working on monoamine neurotransmitters", which include serotonin, dopamine, norepinephrine, epinephrine, and histamine. A monoaminergic, or monoaminergic drug, is a chemical, which functions to directly modulate the ser ...

activity. Other examples are chemicals that modify the electrical signaling inside the body, the most prominent of these being bromides and channel blockers.

Indications

Depressants are used medicinally to relieve the following symptoms: * Anxiety disorders such as: **

Generalized anxiety Generalized anxiety disorder (GAD) is a mental and behavioral disorder, specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily functioni ...

** Social anxiety ** Panic attacks *

Insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy ...

* Obsessive–compulsive disorder *

Seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

s *

Convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a ...

s * Depression * Pain

Types

Alcohol

An alcoholic beverage is a drink that contains alcohol (also known formally as

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a h ...

), an anesthetic that has been used as a

psychoactive drug A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. T ...

for several millennia. Ethanol is the oldest recreational drug still used by humans. Ethanol can cause

alcohol intoxication Alcohol intoxication, also known as alcohol poisoning, commonly described as drunkenness or inebriation, is the negative behavior and physical effects caused by a recent consumption of alcohol. In addition to the toxicity of ethanol, the main ...

when consumed. Alcoholic beverages are divided into three general classes for taxation and regulation of production:

beer Beer is one of the oldest and the most widely consumed type of alcoholic drink in the world, and the third most popular drink overall after water and tea. It is produced by the brewing and fermentation of starches, mainly derived from cer ...

wine Wine is an alcoholic drink typically made from fermented grapes. Yeast consumes the sugar in the grapes and converts it to ethanol and carbon dioxide, releasing heat in the process. Different varieties of grapes and strains of yeasts are ...

s, and spirits (distilled beverages). They are legally consumed in most countries around the world. More than 100 countries have laws regulating their production, sale, and consumption. The most common way to measure intoxication for legal or medical purposes is through

blood alcohol content Blood alcohol content (BAC), also called blood alcohol concentration or blood alcohol level, is a measurement of alcohol intoxication used for legal or medical purposes; it is expressed as mass of alcohol per volume or mass of blood. For example ...

(also called blood alcohol concentration or blood alcohol level). It is usually expressed as a

percentage In mathematics, a percentage (from la, per centum, "by a hundred") is a number or ratio expressed as a fraction of 100. It is often denoted using the percent sign, "%", although the abbreviations "pct.", "pct" and sometimes "pc" are also ...

of alcohol in the

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...

in units of mass of alcohol per volume of blood, or mass of alcohol per mass of blood, depending on the country. For instance, in North America a blood alcohol content of "0.10" or more correctly 0.10 g/dL means that there are 0.10 g of alcohol for every dL of blood (i.e., mass per volume is used there).

Barbiturates

Barbiturates are effective in relieving the conditions that they are designed to address (insomnia, seizures). They are also commonly used for unapproved purposes, are physically addictive, and have serious potential for overdose. In the late 1950s, when many thought that the social cost of barbiturates was beginning to outweigh the medical benefits, a serious search began for a replacement drug. Most people still using barbiturates today do so in the prevention of seizures or in mild form for relief from the symptoms of

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few ho ...

Benzodiazepines

A benzodiazepine (sometimes colloquially "benzo"; often abbreviated "BZD") is a

whose core chemical structure is the fusion of a

benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen ato ...

ring and a diazepine ring. The first such drug, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and made available in 1960 by

Hoffmann–La Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...

, which has also marketed the benzodiazepine diazepam (Valium) since 1963. Benzodiazepines enhance the effect of the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neur ...

gamma-aminobutyric acid (GABA) at the GABA_A receptor, resulting in

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but ...

, hypnotic ( sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties; also seen in the applied pharmacology of high doses of many shorter-acting benzodiazepines are amnesic- dissociative actions. These properties make benzodiazepines useful in treating anxiety, insomnia, agitation, seizures,

muscle spasms A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscl ...

, alcohol withdrawal and as a

premedication Premedication is using medication before some other therapy (usually surgery or chemotherapy) to prepare for that forthcoming therapy. Typical examples include premedicating with a sedative or analgesic before surgery; using prophylactic (prevent ...

for medical or dental procedures. Benzodiazepines are categorized as either short-, intermediate-, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia; longer-acting benzodiazepines are recommended for the treatment of anxiety. In general, benzodiazepines are safe and effective in the short term, although cognitive impairments and

paradoxical effect A paradoxical reaction (or paradoxical effect) is an effect of a chemical substance, such as a medical drug, that is opposite to what would usually be expected. An example of a paradoxical reaction is pain caused by a pain relief medication. Parado ...

s such as aggression or behavioral disinhibition occasionally occur. A minority react reverse and contrary to what would normally be expected. For example, a state of panic may worsen considerably following intake of a benzodiazepine. Long-term use is controversial due to concerns about adverse psychological and physical effects, increased questioning of effectiveness, and, because benzodiazepines are prone to cause

tolerance Tolerance or toleration is the state of tolerating, or putting up with, conditionally. Economics, business, and politics * Toleration Party, a historic political party active in Connecticut * Tolerant Systems, the former name of Veritas Software ...

, physical dependence, and, upon cessation of use after long-term use, benzodiazepine withdrawal syndrome. Due to adverse effects associated with the long-term use of benzodiazepines, withdrawal from benzodiazepines, in general, leads to improved physical and mental health. The elderly are at an increased risk of experiencing both short- and long-term

adverse effects An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a " side effect", when judged to be secondary to a main or therapeutic effect. The term compl ...

. There is controversy concerning the safety of benzodiazepines in pregnancy. While they are not major teratogens, uncertainty remains as to whether they cause cleft palate in a small number of babies and whether neurobehavioural effects occur as a result of prenatal exposure; they are known to cause withdrawal symptoms in the newborn. Benzodiazepines can be taken in overdoses and can cause dangerous deep unconsciousness. However, they are much less toxic than their predecessors, the barbiturates, and death rarely results when a benzodiazepine is the only drug taken; however, when combined with other

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

depressants such as alcohol and

opiate An opiate, in classical pharmacology, is a substance derived from opium. In more modern usage, the term ''opioid'' is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagonist ...

s, the potential for toxicity and fatal overdose increases. Benzodiazepines are commonly misused and taken in combination with other addictive drugs. In addition, all benzodiazepines are listed in Beers List, which is significant in clinical practice.

Cannabis

Cannabis is often considered either in its own unique category or as a mild psychedelic. The chemical compound tetrahydrocannabinol (THC), which is found in cannabis, has many depressant effects such as muscle relaxation, sedation, decreased alertness, and less

tiredness Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

. Contrary to the previous statement, activation of the CB1 receptor by cannabinoids causes an inhibition of GABA, the exact opposite of what central nervous system depressants do.

Carbamates

Carbamates are a class of depressants or " tranquilizers" that are synthesized from urea. Carbamates have anxiolytic, muscle relaxant, anticonvulsant, hypnotic,

antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests that ...

, and

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

effects. It has other uses like muscle tremors, agitation, and alcohol withdrawal. It's muscle relaxant effects are useful for strains, sprains, and muscle injuries together with rest, physical therapy, and other measures. The effects, synthesis and mechanism of action of Carbamates are very similar to barbiturates. There are many different types of Carbamates, some only produce anxiolytic effects and hypnotic effects while some only have anticonvulsant effects.

Side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of Carbamates include

drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asle ...

, dizziness,

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a resul ...

, diarreha,

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

flatulence Flatulence, in humans, is the expulsion of gas from the intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swallowed enviro ...

, liver failure, poor coordination, nystagmus,

abuse Abuse is the improper usage or treatment of a thing, often to unfairly or improperly gain benefit. Abuse can come in many forms, such as: physical or verbal maltreatment, injury, assault, violation, rape, unjust practices, crimes, or other t ...

, dizziness,

weakness Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...

, nervousness,

overstimulation Stimulation is the encouragement of development or the cause of activity generally. For example, "The press provides stimulation of political discourse." An interesting or fun activity can be described as "stimulating", regardless of its physic ...

and dependence. Uncommon but potentially severe adverse reactions include hyper sensivity reactions including Stevens Johnson syndrome, embryo-fetal toxicity, stupor, and coma. Carbamates are fatal in overdose, which is why a lot of them have been replaced with benzodiazepines. It is not recommended to use most Carbamates like Carisoprodol for a long time as physical and psychological dependence does occur. Meprobamate which metabolizes to '' Carisoprodol'' was launched in 1955. It quickly become the first blockbuster psychotropic drug in America becoming popular in Hollywood and gaining fame for its seemingly miraculous effects. It has since been marketed under more than 100 trade names, from Amepromat through Quivet to Zirpon. Carisoprodol, which is still used today mainly for it's muscle relaxant effects has high abuse potential. It's mechanism of action is very similar to barbiturates, alcohol, methaqualone and benzodiazepines. Carsidoprodol allosterically modulates and directly activates the human α1β2γ2 GABAAR ( GABA_A) in the

in a barbiturate-like manner. This causes chloride channels to open, allowing

chloride The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride s ...

to flood into the neuron, slowing down communication betwen neurons; thus slowing down the

nervous system In Biology, biology, the nervous system is the Complex system, highly complex part of an animal that coordinates its Behavior, actions and Sense, sensory information by transmitting action potential, signals to and from different parts of its ...

. Unlike benzodiazpines which increase the frequency of the chloride channel opening, Carisoprodol increase the duration of channel opening when GABA is bound. GABA is the main inhibitory

in the

, which causes its depressant effects. Carbamates are fatal in overdose. Symptoms are similar to a barbiturate overdose. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe ( respiratory depression). An overdose is more likely to be fatal when it is mixed with another depressant that suppresses breathing. Death occurs this is typically due to a lack of breathing. Physical and psychological dependence does happen with long term use of Carbamates; particularly Carisoprodol. Today Carisoprodol is only used short term for muscle pain, particularly back pain. Discontuation after long term use could be very intense and even possibly fatal. Withdrawal can resemble barbiturate, alcohol, or

benzodiazepine withdrawal Benzodiazepine withdrawal syndrome often abbreviated to benzo withdrawal or BZD withdrawal is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines, either medically or recreationally develops a phy ...

, as they all have a similar mechanism of action. Discontinuation symptoms include, confusion, disorientation, delirium,

hallucination A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...

s ( auditory &

visual The visual system comprises the sensory organ (the eye) and parts of the central nervous system (the retina containing photoreceptor cells, the optic nerve, the optic tract and the visual cortex) which gives organisms the sense of sight ...

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy ...

, decreased appetite,

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil Turmoil may refer to: * ''Turmoil'' (1984 video game), a 1984 video game released by Bug-Byte * ''Turmoil'' (2016 video game), a 2016 indie oil tycoon video ...

, psychomotor agitation,

pressured speech Pressure of speech or pressured speech is a tendency to speak rapidly and frenziedly. Pressured speech is motivated by an urgency that may not be apparent to the listener. The speech produced is difficult to interpret. Such speech may be too fas ...

, tremor,

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

s which could be fatal. Carbamates we're popular in the 1950's along with barbiturates. Although they have been slowly phased out; mainly due to the overdose and dependence risks, new derivates still exist. Felbamate is an anticonvulsant that was approved in 1993 that is commonly used today. It is a GABA_A positive allosteric modulator and blocks the NR2B subunit of the NMDA receptor. Some carbamates block sodium channels. Phenprobamate was used as an anxiolytic and is still sometimes used in Europe for general anesthesia and for treating muscle cramps and spasticity. Methocarbamol is a popular drug that is commonly known as Robaxin, that is over the counter in some countries.. It is a carbamate with muscle relaxant effects. Tetrabamate; a is a controversial drug which is a combination of febarbamate,

difebarbamate Difebarbamate (INN) is a tranquilizer of the barbiturate and carbamate families which is used in Europe as a component of a combination drug formulation referred to as tetrabamate (Atrium, Sevrium). See also * Febarbamate Febarbamate ( INN; ...

, and phenobarbital which is marketed in Europe was largely but not completely discontinued. April 4, 1997 after over 30 years of use due to reports of

hepatitis Hepatitis is inflammation of the liver parenchyma, liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), Anorexia (symptom), poor appetite ...

and acute liver failure. The decision to restrict the use of the drug had been long-awaited. Carisoprodol; known as, "Soma" is still commonly used today for it's muscle relaxant effects. It is also very commonly abused around the world. It is a Schedule IV substance in the United States. Famous martial artist and actor

Bruce Lee Bruce Lee (; born Lee Jun-fan, ; November 27, 1940 – July 20, 1973) was a Hong Kong and American martial artist and actor. He was the founder of Jeet Kune Do, a hybrid martial arts philosophy drawing from different combat disciplines th ...

died due to an

allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

to meprobamate. Approved * Carisoprodol/ Meprobamate/ Tybamate (Soma/Miltown, Solacen) (muscle relaxant, anxiolytic, tranquilizer) *

Difebarbamate Difebarbamate (INN) is a tranquilizer of the barbiturate and carbamate families which is used in Europe as a component of a combination drug formulation referred to as tetrabamate (Atrium, Sevrium). See also * Febarbamate Febarbamate ( INN; ...

(Atrium, Sevrium) (tranquilizer) * Emylcamate (Striatran) (anxiolytic and muscle relaxant) *

Ethinamate Ethinamate (Valamin, Valmid) is a short-acting carbamate-derivative sedative-hypnotic medication used to treat insomnia. Regular use leads to drug tolerance, and it is usually not effective for more than 7 days. Prolonged use can lead to dep ...

(Valamin, Valmid) (sedative-hypnotic) * Febarbamate/ Phenobamate (Solium, Tymium) (anxiolytic and tranquilizer) * Felbamate (Felbatol) (anticonvulsant) * Hexapropymate (Merinax) (hypnotic-sedative) * Mebutamate (Capla, Dormate) (anxiolytic, sedative, antihypertensive) * Phenprobamate (Gamaquil, Isotonil) (muscle relaxant, sedative, anxiolytic, anticonvulsant, anesthesia) * Procymate (Equipax) (sedative, anxiolytic) * Styramate (Sinaxamol) (muscle relaxant, anticonvulsant) * Tetrabamate ( febarbamate,

, phenobarbital) (Atrium, G Tril, Sevrium) (anxiety, alcohol withdrawal, muscle tremors, agitation, depression) ''Although a drug may be approved, it does not necessarily mean it is still used today.'' Not approved *

Carisbamate Carisbamate (YKP 509, proposed trade name Comfyde) is an experimental anticonvulsant drug that was under development by Johnson & Johnson Pharmaceutical Research and Development but never marketed. Clinical study A phase II clinical trial in ...

(anticonvulsant) * Clocental (hypnotic) * Cyclarbamate (muscle relaxant and tranquilizer) *

Lorbamate Lorbamate (INN; Abbott-19,957) is a muscle relaxant and tranquilizer A tranquilizer is a drug that is designed for the treatment of anxiety, fear, tension, agitation, and disturbances of the mind, specifically to reduce states of anxiety and ...

(muscle relaxant and tranquilizer) * Nisobamate (tranquilizer) * Pentabamate (tranquilizer)

Gabapentinoids

Gabapentinoids are a unique and relatively novel class of depressants that selectively bind to the auxiliary α₂δ subunit (

CACNA2D1 Voltage-dependent calcium channel subunit alpha-2/delta-1 is a protein that in humans is encoded by the ''CACNA2D1'' gene. This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex ...

) and ( CACNA2D2), site of certain VDCCs, and thereby act as inhibitors of α₂δ subunit-containing Voltage-gated calcium channels. α₂δ is nicknamed the "Gabapentin receptor". At physiologic or resting

membrane potential Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charge ...

, VDCCs are normally closed. They are activated (opened) at depolarized

s and this is the source of the " voltage-gated"

epithet An epithet (, ), also byname, is a descriptive term (word or phrase) known for accompanying or occurring in place of a name and having entered common usage. It has various shades of meaning when applied to seemingly real or fictitious people, di ...

. Gabapentinoids bind to the α1 and α2 sites of the α₂δ subunit family. Gabapentin is the prototypical gabapentinoid. The α₂δ is found on L-type calcium channels, N-type calcium channels, P/Q-type calcium channels, and R-type calcium channels throughout the central and peripheral nervous systems. α₂δ is located on presynaptic neurons and affects

calcium channel A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables ...

trafficking and kinetics, initiates extracellular signaling cascades,

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. ...

and promotes excitatory synaptogenesis through thrombospondin 1 . Gabapentinoids are not direct channel blockers, instead they disrupt the regulatory function of α₂δ and its interactions with other proteins. Most of the effects of gabapentinoids are mediated by the high voltage activated N and P/Q-type calcium channels. P/Q-type calcium channels are mainly found in the

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cere ...

(

Purkinje neurons Purkinje cells, or Purkinje neurons, are a class of GABAergic inhibitory neurons located in the cerebellum. They are named after their discoverer, Czech anatomist Jan Evangelista Purkyně, who characterized the cells in 1839. Structure The ...

) which made be responsible for the ataxic adverse effect of gabapentinoids, while N-type calcium channels are located throughout the central and peripheral nervous systems. N-type calcium channels are mainly responsible for the

effects of gabapentinoids. Ziconotide, a non-gabapentinoid ω- conotoxin

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

binds to the N-type calcium channels and has analgesic effects 1000 times stronger than

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies ('' Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. Ther ...

. Gabapentinoids are selective for the α₂δ site, but non-selective when they bind to the calcium channels complex. They act on the α₂δ site to lower the release of many excitatory and pro- nociceptive

neurochemical A neurochemical is a small organic molecule or peptide that participates in neural activity. The science of neurochemistry studies the functions of neurochemicals. Prominent neurochemicals Neurotransmitters and neuromodulators * Glutamate is ...

s including glutamate, substance P, calcitonin gene-related peptide (CGRP) and more. Gabapentinoids are absorbed from the intestines mainly by the

Large neutral amino acid transporter 1 Large means of great size. Large may also refer to: Mathematics * Arbitrarily large, a phrase in mathematics * Large cardinal, a property of certain transfinite numbers * Large category, a category with a proper class of objects and morphisms (o ...

(LAT1, SLC7A5) and the

Excitatory amino acid transporter 3 Excitatory amino acid transporter 3 (EAAT3), is a protein that in humans is encoded by the ''SLC1A1'' gene. Tissue distribution EAAT3 is expressed on the plasma membrane of neurons, specifically on the dendrites and axon terminals. Function E ...

(EAAT3). They are one of the few drugs that use these amino acid transporters. Gabapentinoids are structurally similar to the Branched-chained amino acids

L-leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- ...

, and L-isoleucine, both of which also bind to the α₂δ site. Branched-chained amino acids like l-leucine, l-isoleucine, and

l-valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotona ...

have many functions in the central nervous system. They modify large neutral amino acid (LNAA) transport at the blood–brain barrier, and reduce the synthesis neurotransmitter of neurotransmitters derived from aromatic-amino acids notably serotonin from

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromati ...

, and

catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol ( benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a ...

s from

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

and phenylalanine. This may be relevant to the

pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemi ...

of gabapentinoids. Gabapentin was designed by researchers at Parke-Davis to be an analogue of the

GABA that could more easily cross the blood–brain barrier and was first described in 1975 by Satzinger and Hartenstein. Gabapentin was first approved for

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

, mainly as an add-on treatment to partial seizures. Gabapentinoids are GABA analogues, but they do not bind to the GABA receptors, do not convert into or another GABA receptor agonist '' in vivo'', and do not directly modulate GABA

transport Transport (in British English), or transportation (in American English), is the intentional movement of humans, animals, and goods from one location to another. Modes of transport include air, land ( rail and road), water, cable, pipel ...

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...

Phenibut Phenibut, sold under the brand names Anvifen, Fenibut, and Noofen among others, is a central nervous system depressant with anxiolytic effects, and is used to treat anxiety, insomnia, and for a variety of other indications. It is usually taken ...

and baclofen, two structurally related compounds are exceptions as they mainly act on the

GABA B receptor GABAB receptors (GABABR) are G-protein coupled receptors for gamma-aminobutyric acid (GABA), therefore making them metabotropic receptors, that are linked via G-proteins to potassium channels. The changing potassium concentrations hyperpol ...

. Also, gabapentin, but not pregabalin, has been found to activate K_vvoltage-gated potassium channels ( KCNQ). Despite this, gabapentinoids mimic GABA activity by inhibiting neurotransmission. Gabapentinoids prevent delivery of the calcium channels to the cell membrane, and disrupt interactions of α₂δ with NMDA receptors,

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the ce ...

neurexin Neurexins (NRXN) are a family of presynaptic cell adhesion proteins that have roles in connecting neurons at the synapse. They are located mostly on the presynaptic membrane and contain a single transmembrane domain. The extracellular doma ...

s, and thrombospondins. Some calcium channel blockers of the dihydropyridine class used for hypertension weakly block α₂δ. Gabapentinoids have anxiolytic, anticonvulsant, antiallodynic, and antinociceptive properties. Pregabalin and gabapentin are used in

, mainly partial seizures (focal). Gabapentinoids are not effective for generalized seizures. They are also used for postherpetic neuralgia, neuropathic pain associated with diabetic neuropathy,

fibromyalgia Fibromyalgia (FM) is a medical condition defined by the presence of chronic widespread pain, fatigue, waking unrefreshed, cognitive symptoms, lower abdominal pain or cramps, and depression. Other symptoms include insomnia and a general hype ...

, generalized anxiety disorder, and restless legs syndrome. Pregabalin and gabapentin have many off-label uses including

, Alcohol and opioid withdrawal, smoking cessation, social anxiety disorder,

bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...

, attention deficit hyperactivity disorder,

chronic pain Chronic pain is classified as pain that lasts longer than three to six months. In medicine, the distinction between acute and chronic pain is sometimes determined by the amount of time since onset. Two commonly used markers are pain that continues ...

, hot flashes, tinnutus,

s and more. Baclofen is primarily used for the treatment of spastic movement disorders, especially in instances of spinal cord injury,

cerebral palsy Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, spasticity, stiff muscles, Paresis, weak muscles, and tremors. There may be p ...

, and multiple sclerosis. Phenibut is used in Russia, Ukraine, Belarus and Latvia to treat anxiety and to improve sleep, as in the treatment of insomnia. It is also used for various other indications, including the treatment of asthenia, depression,

alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomina ...

, alcohol withdrawal syndrome, post-traumatic stress disorder, stuttering, tics, vestibular disorders,

Ménière's disease Ménière's disease (MD) is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Typically, only one ear is affected initi ...

, dizziness, for the prevention of motion sickness, and for the prevention of anxiety before or after surgical procedures or painful diagnostic tests. Phenibut, like other GABA B agonists, is also sometimes used by body builders to increase human growth hormone.

Reuters Reuters ( ) is a news agency owned by Thomson Reuters Corporation. It employs around 2,500 journalists and 600 photojournalists in about 200 locations worldwide. Reuters is one of the largest news agencies in the world. The agency was est ...

reported on 25 March 2010, that " Pfizer Inc violated a United States racketeering law by improperly promoting the epilepsy drug Neurontin (gabapentin). Under the Racketeer Influenced and Corrupt Organizations Act the penalty is automatically tripled, so the finding will cost Pfizer $141 million." The case stems from a claim from Kaiser Foundation Health Plan Inc. that "it was misled into believing Neurontin was effective for off-label treatment of migraines, bipolar disorder and other conditions. Pfizer argued that Kaiser physicians still recommend the drug for those uses", and that "the insurer's website also still lists Neurontin as a drug for neuropathic pain." In some cases, gabapentinoids are

d and provide similar effects to alcohol, benzodiazepines and gamma-hydroxybutyric acid (GHB). The FDA placed a black box warning on Neurontin (gabapentin), and Lyrica (pregabalin), for serious breathing problems. Mixing gabapentinoids with

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioi ...

s, benzodiazepines, barbiturates, GHB, alcohol, or any other depressant is potentially deadly. Common side effects of gabapentinoids include

, dizziness,

, increased appetite, urinary retention,

shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...

, involuntary eye movements ( nystagmus), memory issues, uncontrollable jerking motions, auditory hallucinations,

erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of ma ...

, and myoclonic seizures. An overdose of gabapentinoids usually consists of severe drowsiness, severe ataxia,

blurred vision Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details. Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressu ...

, slurred speech, severe uncontrollable jerking motions, and

. Like most anticonvulsants, pregabalin and gabapentin have an increased risk of suicidal thoughts and behaviors. Gabapentinoids, like all calcium channel blockers are known to cause angioedema. Taking them with an ACE inhibitor can increase the toxic effects of Gabapentinoids. They may also enhance the fluid-retaining effect of certain anti-diabetic agents ( thiazolidinediones). It is not known if they cause gingival enlargement like other calcium channel blockers. Gabapentinoids are excreted by the kidney mostly in their original form. Gabapentinoids can build up in the body when someone has

renal failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

. This usually presents itself as

myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, i ...

, and an

altered mental state An altered state of consciousness (ASC), also called altered state of mind or mind alteration, is any condition which is significantly different from a normal waking state. By 1892, the expression was in use in relation to hypnosis, though there ...

. It is unclear if it is safe to use Gabapentinoids during pregnancy with some studies showing potential harm. Physical or

physiological dependence Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certain ...

does occur during long-term use of gabapentinoids. Following abrupt or rapid discontinuation of pregabalin and gabapentin people report withdrawal symptoms like insomnia,

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin ...

, flu-like symptoms, anxiety, depression,

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

hyperhidrosis Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psycholog ...

s, psychomotor agitation, confusion, disorientation, and gastrointestinal complaints. Acute withdrawal from baclofen and phenibut may also cause auditory and visual

s, and acute psychosis. Baclofen withdrawal can be more intense if it is administered intrathecally or for long periods of time. If Baclofen or Phenibut is used for long periods of time it can resemble intense benzodiazepine, GHB or alcohol withdrawal. To minimize withdrawal symptoms Baclofen or Phenibut should be tapered down slowly. Abrupt withdrawal from

or Baclofen could be possibly be life-threatening, because of it’s mechanism of action. Abrupt withdrawal can cause rebound seizures and severe agitation. *

Gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diab ...

(Neurontin) *

Gabapentin Enacarbil Gabapentin enacarbil (Horizant () (), Regnite (in Japan)) is an anticonvulsant and analgesic drug of the gabapentinoid class, and a prodrug to gabapentin. It was designed for increased oral bioavailability over gabapentin, and human trials s ...

(Horizant, Regnite) * Gabapentin Extended-Release (Gralise) * Pregabalin (Lyrica) *

(Anvifen, Fenibut, Noofen) * Baclofen (Lioresal) *

Mirogabalin Mirogabalin (brand name Tarlige; developmental code name DS-5565) is a medication developed by Daiichi Sankyo, a gabapentinoid. Gabapentin and pregabalin are also members of this class. As a gabapentinoid, mirogabalin binds to the α2δ subu ...

(Tarlige) (Japan Only) Not approved: * Imagabalin *

Tolibut Tolibut, also known as 3-(''p''-tolyl)-4-aminobutyric acid (or β-(4-methylphenyl)-GABA), is drug that was developed in Russia. It is an analogue of γ-aminobutyric acid (GABA) (that is, a GABA analogue) and is the 4-methyl analogue of phenibu ...

* 4-Flurophenibut * HSK16149 * Trans-4 and cis-4- 8Ffluorogabapentin (α2δ

PET Imaging Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...

) * 4-Methylpregabalin *

PD-217,014 PD-217,014 is a drug developed by Pfizer and related to gabapentin, which similarly binds to the α2δ calcium channels ( 1 and 2). It was developed as a potentially more potent successor to gabapentin and pregabalin, along with several other ...

Atagabalin Atagabalin (PD-0200,390) is a drug developed by Pfizer and related to gabapentin, which similarly binds to the α2δ calcium channel A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synon ...

Arbaclofen Arbaclofen placarbil ( , also known as XP19986) is a prodrug of ''R''-baclofen. Arbaclofen placarbil possesses more favorable pharmacokinetic profile than baclofen, with less fluctuations in plasma drug levels. It was being developed as a potent ...

* Saclofen Endogenous (Not Gabapentinoids, endogenous BCAA amino acids that bind to α₂δ: *

Calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

* Isoleucine * Leucine * Valine * Aspartate Other α2δ ligands: * Phenylalanine * NP-118809 * Gababutin * Ziconotide (Approved for pain) *

Ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a h ...

Dextrothyroxine Dextrothyroxine (trade name Choloxin) is a dextrorotary isomer of thyroxine. It saw research as a cholesterol-lowering drug but was pulled due to cardiac side-effects. It increases hepatic lipase which in turn improves utilization of triglycerid ...

( Agonist of α2δ instead of inhibiting it) * Ethioninie * Suloctidil *

Terodiline Terodiline is a drug used in urology as an antispasmodic. It relaxes the smooth muscle and used to reduce bladder tone in treatment of urinary frequency and incontinence. Muscle relaxation caused by terodiline, is probably due to its anticholi ...

* Bepridil

Opioids

Contrary to popular misconception,

are not depressants in the classical sense. They do produce central nervous system depression, however, they also excite certain areas of the central nervous system. To remain true to the term 'depressant' – opioids cannot be classified as such. For opioid agonists and

opium Opium (or poppy tears, scientific name: ''Lachryma papaveris'') is dried latex obtained from the seed capsules of the opium poppy '' Papaver somniferum''. Approximately 12 percent of opium is made up of the analgesic alkaloid morphine, which ...

derivatives The derivative of a function is the rate of change of the function's output relative to its input value. Derivative may also refer to: In mathematics and economics *Brzozowski derivative in the theory of formal languages *Formal derivative, an ...

, these are classified differently.

Analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

or narcotic correctly identifies these drugs. However, they do have depressant actions nonetheless. *

Morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies ('' Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. Ther ...

* Heroin * Codeine *

Hydrocodone Hydrocodone, also known as dihydrocodeinone, is an opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe en ...

* Oxycodone * Methadone

Piperidinediones

Piperidinediones are a class of depressants that are not used anymore. There are Piperidinediones that are used for other purposes like

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...

br>
https://books.google.ca/books?id=tsjrCAAAQBAJ&pg=PA14&redir_esc=y#v=onepage&q&f=fals

. The Piperidinedione class is very structurally similar to barbiturates. Piperidinediones inclide Glutethimide, Methyprylon,

Pyrithyldione Pyrithyldione (Presidon, Persedon) is a psychoactive drug invented in 1949. An improved method of manufacture was patented by Roche in 1959. It was used as a hypnotic or sedative and presumed to be less toxic than barbiturates. Today, this subst ...

, Glutarimide, and Aminoglutethimide. The first 3, (Glutethimide, Methyprylon, Pyrithyldione) are central nervous depressants. The Piperidinedione depressants, specifcally Glutethimide is a positive modulator of the GABA_A anion channel. The drug increases inhibitory GABAergic tone and causes neuro-inhibition of the cortical and limbic systems, observed clinically as a sedative-hypnotic effec

Glutethimide is also a potent inhibitor of the CYP2D6, CYP 2D6 enzyme in the liver. This enzyme is responsible for converting many drugs from

beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack ( secondary prevention). They are ...

s to

s and

s. Due to its effects on the conversion of opioids, it was highly abused and mixed with opioids like codeine. Codeine needs to get metabolized to

in the liver to have its psychoactive and

effects. Mixing codeine with the Piperidinedione Glutethimide allowed more codeine to be converted into morphine in the body; this increasing its effect. This was known as "hits", "cibas and codeine", "Dors and 4s". Glutethimide was believed to be safer than barbiturates, but many people died from the drug. Demand was high in the United States at one point. Production of glutethimide was discontinued in the US in 1993 and in several eastern European countries, most notably Hungary, in 2006. Glutethimide

withdrawal Withdrawal means "an act of taking out" and may refer to: * Anchoresis (withdrawal from the world for religious or ethical reasons) * '' Coitus interruptus'' (the withdrawal method) * Drug withdrawal * Social withdrawal * Taking of money from ...

is intense and resembles barbiturate withdrawal. It features

s and delirium; typical of a depressant withdrawal. In the 1970s, there were reports of neonatal withdrawal from glutethimide. Infants born to mothers addicted to glutethimide responded well initially, then had recurrence of symptoms about 5 days later, including overactivity, restlessness, tremors,

hyperreflexia Hyperreflexia is overactive or overresponsive bodily reflexes. Examples of this include twitching and spastic tendencies, which indicate upper disease of the upper motor neurons and the lessening or loss of control ordinarily exerted by highe ...

, hypotonus,

vasomotor instability Hot flashes (also known as hot flushes) are a form of Flushing (physiology), flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating an ...

, incessant crying, and general irritability. Glutethimide withdrawal featured severe agitation, tremor and

s which could be fatal. Overdose causes stupor or coma and respiratory depression. * Methyprylon (Dimerin, Methyprylone, Noctan, Noludar) * Pyrithyldione (Presidon, Pyridion, Pyridione, Pyrithyldion, Pyrithyldione) * Piperidione (Ascron, Dihyprylon, Dihyprylone, Sedulon, Tusseval) (Withdrawan before approval) * Glutethimide (Doriden)

Quinazolinone

Quinazolinones are a class of depressants that are rarely used anymore. Quinazolinone have powerful sedative, hypnotic, and anxiolytic effects. Quinazolinones structures are very similar to some antibiotics. Quinazolines main mechanism of action is binding to the GABA_A receptor. It does not bind to the

, barbiturate, neurosteroid, or benzodiazepine site. Instead it binds on a site right betwen the GABRB2 (β2) and (α1) GABRA1 proteins on the GABA_A receptor. The anesthetic etomidate and Anticonvulsant loreclezole may also bind to this site. Overdose on Quinazolinone sometimes causes effects that are the opposite of Quinazolinone like sedation. Overdose consists of

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

, kidney failure, delirium, hypertonia, coma, myoclonic twitches, somnolence,

, muscular hyperactivity,

agitated delirium Excited delirium (ExDS), also known as agitated delirium (AgDS), is a controversial diagnosis sometimes characterized as a potentially fatal state of extreme agitation and delirium. It is typically diagnosed postmortem in young adult males, dispr ...

, and tonic-clonic seizures. In 1982 2,764 people visited US emergency rooms from overdosing on Quinazolinones, specifically Methaqualone. Mixing Quinazolines with another depressant is possibly fatal. Death from a Quinazolinone overdose is usually caused by death through

cardiac The heart is a muscular organ found in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon di ...

or respiratory arrest. Overdose resembles barbiturate/ carbamate overdose. Quinazolinones

occurs when someone has become dependent on a quinazolinone substance and stops using them. Quinazolinone withdrawal resembles

, barbiturate, benzodiazepine and carbamate withdrawal. It usually consists of restlessness,

and

, decreased appetite,

, tremor,

s, delirium, confusion, seizures; which could cause death, EEG photoparoxysmal response, myoclonic twitches,

fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

, and irritability. Methaqualone hydrochloride, a Quinazolinone anxiolytic and hypnotic is referred to as "quaaludes" "ludes" and "disco biscuits". Methaqualone was very commonly abused in the western world during the 1960s and 1970s. Methaqualone was mainly prescribed for

as it was thought to be safer than barbiturates and carbamate

Methaqualone became highly abused by people and celebrities after it's introduction in 1965. Methaqualone was first synthesized in India in 1951 by Indra Kishore Kacker and Syed Husain Zaheer, who were conducting research on finding new antimalarial medications. The drug name "Quaalude" (Methaqualone) is a

portmanteau A portmanteau word, or portmanteau (, ) is a blend of wordspsychological addictiveness, widespread

, and illegal recreational use. Non-benzodiazepines, and benzodiazepines are now uses to treat

instead. Methaqualone is now a schedule I substance. Some quinazolinone analogues are still sold online. They come with risks of

s. Large doses of Methaqualone cause

, disinhibition, increased sexuality,

sociability Social behavior is behavior among two or more organisms within the same species, and encompasses any behavior in which one member affects the other. This is due to an interaction among those members. Social behavior can be seen as similar to an ...

, muscle relaxation, anxiolysis, and sedation. Today Methaqualone is widely abused in

South Africa South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring count ...

. Many celebrities have used Quinazolinone; specifically Methaqualone. Bill Cosby admitted to casual sex involving recreational use of Methaqualone (Quaaludes). 18 year old actor Anissa Jones died at 18 from an overdose of cocaine, PCP, Methaqualone, and the barbiturate Seconal. Billy Murcia a drummer for the rock band New York Dolls died at 21 when he drowned in a bathtub while overdosing on heroin and Methaqualone. Cloroqualone was a Quinazolinone that binded to the GABA_A and sigma-1 receptor. It had useful cough suppressant effects and weaker sedative effects than Methaqualone. But it was withdrawan due to its potential for abuse and overdose. Diproqualone is a Quinazolinone that is still used today. Diproqualone has

, anxiolytic,

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provide ...

and

properties, resulting from its agonist activity at the β subtype of the GABA_a receptor, antagonist activity at all histamine receptors, inhibition of the cyclooxygenase-1 enzyme, and possibly its agonist activity at both the sigma-1 receptor and sigma-2 receptor. Diproqualone is used primarily for the treatment of

inflammatory pain Inflammatory may refer to: * Inflammation, a biological response to harmful stimuli * The word ''inflammatory'' is also used to refer literally to fire and flammability, and figuratively in relation to comments that are provocative and arouse p ...

associated with

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the ...

and

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and ...

, and more rarely for treating

and neuralgia. Diproqualone is the only analogue of methaqualone that is still in widespread clinical use, due to its useful

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as ...

and

effects in addition to the

and anxiolytic actions common to other drugs of this class. There are still some concerns about the potential of diproqualone for

and overdose, and so it is not sold as a pure drug but only as the camphosulfonate salt in combination mixtures with other medicines such as ethenzamide. Etaqualone is a quinazolinone-class depressant. It has

, hypnotic, muscle relaxant and central nervous system depressant properties. It was highly abused, and had high risk for overdose. Users would snort or smoke the free base Etaqualone hydrochloride salt. Methylmethaqualone is an analogue of Methaqualone with similar hypnotic and

effects. Methylmethaqualone differs from methaqualone by 4-methylation on the phenyl ring. It produces

convulsions A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a ...

at only slightly above the effective sedative dose. It would appear that this compound was sold on the black market in Germany as a

designer drug A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Des ...

analogue of methaqualone. Nitromethaqualone is a quinazolinone depressant with 10x more powerful hypnotic and

effects than Methaqualone. Quinazolinone's: * Alfoqualone (Arofuto) * Cloroqualone * Diproqualone * Etaqualone (Aolan, Athinazone, Ethinazone) * Mebroqualone (MBQ) * Mecloqualone (Nubarene, Casfen) * Methaqualone (Quaalude, Sopor, Mandrax) * Methylmethaqualone * Nitromethaqualone * SL-164 (Dicloqualone, DCQ)

Miscellaneous

* Alpha and

s ( carvedilol, propranolol, atenolol, etc.) *

Anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous syste ...

s ( atropine, hyoscyamine, scopolamine, etc.) * Anticonvulsants ( topiramate,

carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medi ...

, lamotrigine, etc.) *

Antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provide ...

s ( diphenhydramine, doxylamine, promethazine, etc.) *

Antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range o ...

s ( haloperidol, chlorpromazine,

clozapine Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate resp ...

, etc.) * Hypnotics ( zolpidem, zopiclone, chloral hydrate, eszopiclone, etc.) * Muscle relaxants (baclofen, phenibut, carisoprodol, cyclobenzaprine, etc.) *

Sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but ...

s (

gamma-hydroxybutyrate ''gamma''-Hydroxybutyric acid (or γ-hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid) is a naturally occurring neurotransmitter and a depressant drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. ...

, etc.)

Methods of intake

Combining multiple depressants can be very dangerous because the central nervous system's depressive properties have been proposed to increase exponentially instead of linearly. This characteristic makes depressants a common choice for deliberate overdoses in the case of

suicide Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and ...

. The use of alcohol or benzodiazepines along with the usual dose of heroin is often the cause of overdose deaths in opiate addicts.

References

External links

Painfully Obvious – A Community Resource

Fact sheets and Harm Reduction Strategies About Depressants and Other Recreational Drugs

U.S. Department of Human and Health Services: Drug Categories for Substances of Abuse

* National Institute on Drug Abuse:
NIDA for Teens: Prescription Depressant Medications
. {{Recreational drug use Psychoactive drugs Drugs acting on the nervous system Health effects of alcohol