Phenelzine, sold under the brand name Nardil among others, is a non-selective and irreversible

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a drug class, class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressa ...

(MAOI) of the

hydrazine Hydrazine is an inorganic compound with the chemical formula . It is a simple pnictogen hydride, and is a colourless flammable liquid with an ammonia-like odour. Hydrazine is highly hazardous unless handled in solution as, for example, hydraz ...

family which is primarily used as an

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

and

anxiolytic An anxiolytic (; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

to treat depression and

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

. Along with

tranylcypromine Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used a ...

and

isocarboxazid Isocarboxazid, sold under the brand name Marplan among others, is a non-selective irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class used as an antidepressant. Along with phenelzine and tranylcypromine, it is one of only thre ...

, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use. Synthesis of phenelzine was first described by

Emil Votoček Emil Votoček (5 October 1872 – 11 October 1950) was a Czech chemist, composer and music theorist. He is noted for his chemistry textbooks and multilingual dictionaries in both chemistry and music. Chemistry career Votoček studied at the ...

and Otakar Leminger in 1932.

Medical uses

Phenelzine is primarily used in the treatment of

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive depression (mood), low mood, low self-esteem, and anhedonia, loss of interest or pleasure in normally ...

. Patients with

atypical depression ''Atypical'' is an American comedy-drama television series created by Robia Rashid for Netflix. The series takes place in Connecticut, and focuses on the life of 18-year-old Samuel "Sam" Gardner ( Keir Gilchrist), who is autistic. The first ...

respond particularly well to phenelzine. The medication is also useful in

treatment-resistant depression Treatment-resistant depression (TRD) is often defined as major depressive disorder in which an affected person does not respond adequately to at least two different antidepressant medications at an adequate dose and for an adequate duration. Inad ...

, where patients do not respond favorably to first and second-line treatments for depression. In addition to being a recognized treatment for major depressive disorder, phenelzine is also effective in treating

dysthymia Dysthymia ( ), known as persistent depressive disorder (PDD) in the DSM-5-TR and dysthymic disorder in ICD-11, is a psychiatric condition marked by symptoms that are similar to those of major depressive disorder, but which persist for at leas ...

bipolar depression Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that each last from days to weeks, and in some cases months. If the elevated m ...

panic disorder Panic disorder is a mental disorder, specifically an anxiety disorder, characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, shortness of breath ...

social anxiety disorder Social anxiety disorder (SAD), also known as social phobia, is an anxiety disorder characterized by sentiments of fear and anxiety in social situations, causing considerable distress and impairing ability to function in at least some asp ...

bulimia nervosa Bulimia nervosa, also known simply as bulimia, is an eating disorder characterized by binge eating (eating large quantities of food in a short period of time, often feeling out of control) followed by compensatory behaviors, such as self-indu ...

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...

(PTSD), and

obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental disorder in which an individual has intrusive thoughts (an ''obsession'') and feels the need to perform certain routines (''Compulsive behavior, compulsions'') repeatedly to relieve the dis ...

(OCD).

Side effects

Common side effects of phenelzine may include

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...

blurry 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 pressure ...

dry mouth Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause. This symptom is very common and is o ...

headache A headache, also known as cephalalgia, 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 (mood), depression in those with severe ...

lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness, or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overw ...

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

somnolence 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 aslee ...

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

anorexia Anorexia nervosa (AN), often referred to simply as anorexia, is an eating disorder characterized by Calorie restriction, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. Individuals wit ...

weight gain Weight gain is an increase in body weight. This can involve an increase in muscle mass, fat deposits, excess fluids such as water or other factors. Weight gain can be a symptom of a serious medical condition. Description Weight gain occurs ...

loss Loss may refer to: *Economic loss *Grief, an emotional response to loss **Animal loss, grief over the loss of an animal Mathematics, science, and technology * Angular misalignment loss, power loss caused by the deviation from optimum angular al ...

small fiber peripheral neuropathy Small fiber peripheral neuropathy is a type of peripheral neuropathy that occurs from damage to the small unmyelinated and myelinated peripheral nerve fibers. These fibers, categorized as C fibers and small Aδ fibers, are present in skin, perip ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

and

vomiting Vomiting (also known as emesis, puking and throwing up) is the 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, gastroenteritis, pre ...

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...

urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include urinary incont ...

mydriasis Mydriasis is the Pupillary dilation, dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, Physical trauma, trauma, or the use of c ...

muscle tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fac ...

hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...

sweating Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distributed over much of the ...

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

paresthesia Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or Chronic condition, chronic and has many possible underlying causes. Paresthesia is usually p ...

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

sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction ...

(consisting of loss of

libido In psychology, libido (; ) is psychic drive or energy, usually conceived of as sexual in nature, but sometimes conceived of as including other forms of desire. The term ''libido'' was originally developed by Sigmund Freud, the pioneering origin ...

and

anorgasmia Anorgasmia is a type of sexual dysfunction in which a person cannot achieve orgasm despite adequate sexual stimulation. Anorgasmia is far more common in females (4.6%) than in males and is especially rare in younger men. The problem is greater in ...

). Rare side effects usually only seen in susceptible individuals may include

hypomania Hypomania (literally "under mania" or "less than mania") is a Psychiatry, psychiatric Abnormality (behavior), behavioral syndrome characterized essentially by an apparently non-contextual elevation of Mood (psychology), mood (i.e., euphoria) th ...

mania Mania, also known as manic syndrome, is a Psychiatry, psychiatric Abnormality (behavior), behavioral syndrome defined as a state of Abnormality (behavior), abnormally elevated arousal, affect (psychology), affect, and energy level. During a mani ...

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

, and

acute liver failure Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complicati ...

, the last of which is usually only seen in people with pre-existing

liver damage Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground glas ...

old age Old age is the range of ages for people nearing and surpassing life expectancy. People who are of old age are also referred to as: old people, elderly, elders, senior citizens, seniors or older adults. Old age is not a definite biological sta ...

long-term effects of alcohol consumption The long-term effects of alcohol consumption on health are predominantly detrimental, with the severity and range of harms generally increasing with the cumulative amount of alcohol consumed over a lifetime. The extent of these effects varies depen ...

, or

viral infection A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Examples include the common cold, gastroenteritis, COVID-19, t ...

Interactions

The MAOIs have certain dietary restrictions and drug interactions. A

hypertensive crisis Severely elevated blood pressure (equal to or greater than 180 mmHg systolic or 120 mmHg diastolic) is referred to as a hypertensive crisis (sometimes termed malignant or accelerated hypertension), due to the high risk of complications. People ...

may result from the overconsumption of

tyramine Tyramine ( ) (also spelled tyramin), also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the bl ...

-containing foods, although it is a rare occurrence.

Serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

may result from an interaction with certain drugs which increase serotonin activity such as

selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

serotonin releasing agent A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter ...

s, and

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

s. Phenelzine has also been linked to vitamin B₆

deficiency A deficiency is generally a lack of something. It may also refer to: *A deficient number, in mathematics, a number ''n'' for which ''σ''(''n'') < 2''n'' * GABA-transaminase have been shown to be dependent upon vitamin B₆; and may be involved in a potentially related process, since the phenelzine metabolite phenylethylidenehydrazine (PEH) is a GABA-transaminase inhibitor. Both phenelzine and vitamin B₆ are rendered inactive upon these reactions occurring. The pyridoxine form of B₆ is recommended for supplementation, since this form has been shown to reduce

toxicity from phenelzine and, in contrast, the

pyridoxal Pyridoxal (PL) is one form of vitamin B6. Some medically relevant bacteria, such as those in the genera '' Granulicatella'' and '' Abiotrophia'', require pyridoxal for growth. This nutritional requirement can lead to the culture phenomenon of s ...

form has been shown to increase the toxicity of hydrazines.

Pharmacology

Pharmacodynamics

Phenelzine is a non-selective and irreversible inhibitor of the

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The fi ...

(MAO). It inhibits both of the respective

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

s of MAO,

MAO-A Monoamine oxidase A, also known as MAO-A, is an enzyme ( E.C. 1.4.3.4) that in humans is encoded by the ''MAOA'' gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamin ...

and

MAO-B Monoamine oxidase B (MAO-B) is an enzyme that in humans is encoded by the ''MAOB'' gene. The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the outer mitochondrial membrane. It catalyze ...

, and does so almost equally, with a slight preference for the former. By inhibiting MAO, phenelzine prevents the breakdown of the

monoamine Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines are ...

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

melatonin Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

, and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

, as well as the

trace amine Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to ...

neuromodulator Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a secon ...

s such as

phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...

octopamine Octopamine (OA), also known as ''para''-octopamine and norsynephrine among synonyms, is an organic chemical closely related to norepinephrine, and synthesized biologically by a homologous pathway. Octopamine is often considered the major "fig ...

, and

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

. This leads to an increase in the

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

s of these

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 th ...

s and, therefore, an alteration in

neurochemistry Neurochemistry is the study of chemicals, including neurotransmitters and other molecules such as psychopharmaceuticals and neuropeptides, that control and influence the physiology of the nervous system. This particular field within neuroscience e ...

and

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron ...

. This action is thought to be the primary mediator in phenelzine's therapeutic benefits. Phenelzine and its metabolites also inhibit at least two other enzymes to a lesser extent, of which are

alanine transaminase Alanine aminotransferase (ALT or ALAT), formerly alanine transaminase (ALT), and even earlier referred to as serum glutamate-pyruvate transaminase (GPT) or serum glutamic-pyruvic transaminase (SGPT), is a transaminase enzyme () that was first c ...

(ALA-T), and γ-aminobutyric acid transaminase (GABA-T), the latter of which is not caused by phenelzine itself, but by a phenelzine metabolite phenylethylidenehydrazine (PEH). By inhibiting ALA-T and GABA-T, phenelzine causes an increase in the

alanine Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group sid ...

and

GABA GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

levels in the brain and body. GABA is the major

inhibitory An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a Chemical synapse, postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Inc ...

neurotransmitter in the

mammalian A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

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

, and is very important for the normal suppression of anxiety, stress, and depression. Phenelzine's action in increasing GABA concentrations may significantly contribute to its antidepressant, and especially, anxiolytic/antipanic properties, the latter of which have been considered superior to those of other antidepressants. As for ALA-T inhibition, though the consequences of disabling this enzyme are currently not well understood, there is some evidence to suggest that it is this action of the hydrazines (including phenelzine) which may be responsible for the occasional incidence of

and

liver failure Liver failure is the inability of the liver to perform its normal synthetic and metabolic functions as part of normal physiology. Two forms are recognised, acute and chronic (cirrhosis). Recently, a third form of liver failure known as acute- ...

. Phenelzine has also been shown to metabolize to phenethylamine (PEA). PEA acts as a

releasing agent A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrati ...

of norepinephrine and dopamine, which occurs in a similar manner to

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

by being taken up into vesicles, displacing and causing the release of those monoamines, and reversing monoamine flux through their respective transporters (though with markedly shorter pharmacokinetics). Like many other antidepressants, phenelzine usually requires several weeks of treatment to achieve full therapeutic effects. The reason for this delay is not fully understood. Still, it is believed to be due to many factors, including achieving steady-state levels of MAO inhibition and the resulting adaptations in mean neurotransmitter levels, the possibility of necessary desensitization of

autoreceptor An autoreceptor is a type of Receptor (biochemistry), receptor located in the cell membrane, membranes of neuron, nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or ...

s which generally inhibit the release of neurotransmitters like serotonin and dopamine, and also the upregulation of enzymes such as

serotonin N-acetyltransferase Aralkylamine ''N''-acetyltransferase (AANAT) (), also known as arylalkylamine ''N''-acetyltransferase or serotonin ''N''-acetyltransferase (SNAT), is an enzyme that is involved in the day/night rhythmic production of melatonin, by modification ...

. Typically, a therapeutic response to MAOIs is associated with an inhibition of at least 80-85% of monoamine oxidase activity.

Pharmacokinetics

Phenelzine is administered orally in the form of phenelzine sulfate and is rapidly absorbed from the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

. The time to peak plasma concentration is 43 minutes, and the half-life is 11.6 hours. Unlike most other drugs, phenelzine irreversibly disables MAO. As a result, it does not necessarily need to be present in the blood at all times for its effects to be sustained. Because of this, upon phenelzine treatment being ceased, its effects typically do not wear off until the body replenishes its enzyme stores, a process which can take as long as 2–3 weeks. Phenelzine is

metabolized Metabolism (, from ''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 cellular processes; the co ...

primarily in the liver, and its

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s are excreted in the urine. Oxidation is the primary routine of metabolism, and the major metabolites are phenylacetic acid and parahydroxyphenylacetic acid, recovered as about 73% of the excreted dose of phenelzine in the urine over 96 hours after single doses. Acetylation to N²-acetylphenelzine is a minor pathway. Phenelzine may also interact with cytochrome P450 enzymes, inactivating these enzymes through the formation of a heme adduct. Two other minor metabolites of phenelzine, as mentioned above, include phenylethylidenehydrazine and phenethylamine.

Chemistry

Phenelzine, also known as 2-phenylethylhydrazine or phenylethylamine hydrazide, is a

and

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

. It is the

hydrazide Hydrazides in organic chemistry are a class of organic compounds with the formula where R is acyl (), sulfonyl (), phosphoryl (), phosphonyl () and similar groups (chalcogen analogs are included, for example sulfur analogs called thiohydrazide ...

β-phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...

and can also be referred to as ''N''-aminophenethylamine. Close analogues of phenelzine include the

and hydrazine derivatives

pheniprazine Pheniprazine, formerly sold under the brand names Catron and Cavodil, is an irreversible and non-selective monoamine oxidase inhibitor (MAOI) of the hydrazine group that was used as an antidepressant to treat depression in the 1960s. It was a ...

(α-methylphenelzine; the corresponding

analogue) and

metfendrazine Metfendrazine (developmental code names HM-11, MO-482), also known as methphendrazine, is an irreversible and nonselective monoamine oxidase inhibitor (MAOI) of the hydrazine family. It was investigated as an antidepressant, but was never marke ...

(α,''N''-dimethylphenelzine; the corresponding

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

analogue), among others.

Research

Phenelzine showed promise in a phase II clinical trial from March 2020 in treating

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

. * Phenelzine has also been shown to have neuroprotective effects in animal models.

References

{{Portal bar , Medicine GABA transaminase inhibitors Hepatotoxins Monoamine oxidase inhibitors Phenethylhydrazines Withdrawn drugs