Methcathinone (α-

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

amino In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

propiophenone Propiophenone (shorthand: benzoylethane or BzEt) is an aryl ketone. It is a colorless, sweet-smelling liquid that is insoluble in water, but miscible with organic solvents. It is used in the preparation of other compounds. Production Propiophenon ...

or ephedrone) (sometimes called "cat" or "jeff" or "catnip" or "M-Kat" or "kat" or "intash") is a

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 ...

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

and

psychoactive A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

, a substituted

cathinone Cathinone (; also known as β-ketoamphetamine) is a monoamine alkaloid found in the shrub ''Catha edulis'' (khat) and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the main contributor to t ...

. It is used as a

recreational drug Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an Sub ...

due to its potent stimulant and

euphoric 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 danci ...

effects and is considered to be

addictive Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use can ...

, with both physical and psychological withdrawal occurring if its use is discontinued after prolonged or high-dosage administration. It is usually snorted, but can be smoked, injected, or taken orally. Methcathinone is listed as a

Schedule I controlled substance The Controlled Substances Act (CSA) is the statute establishing federal U.S. drug policy under which the manufacture, importation, possession, use, and distribution of certain substances is regulated. It was passed by the 91st United State ...

by the

Convention on Psychotropic Substances The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamine-type stimulants, barbiturates, benzodiazepines, and psychedelics signed in Vienna, Austria on 21 February ...

and the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...

, and as such it is not considered to be safe or effective in the treatment, diagnosis, prevention, or cure of any disease, and has no approved medical use. Possession and distribution of methcathinone for the purpose of human consumption is illegal under any/all circumstances in the United States and is either illegal or highly regulated in most jurisdictions worldwide.

History

Methcathinone was first synthesized in 1928 in the United States and was patented by

Parke-Davis Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although Parke, Davis & Co. is no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history. In 1970 ...

in 1957. It was used in the

Soviet Union The Union of Soviet Socialist Republics. (USSR), commonly known as the Soviet Union, was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 until Dissolution of the Soviet ...

during the 1930s and 1940s as an

anti-depressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia, sexua ...

(under the name ''Эфедрон''—''ephedrone''). Methcathinone has long been used as a drug of abuse in the

and

Russia Russia, or the Russian Federation, is a country spanning Eastern Europe and North Asia. It is the list of countries and dependencies by area, largest country in the world, and extends across Time in Russia, eleven time zones, sharing Borders ...

. Circa 1994, the United States government recommended to the

UN Secretary-General The secretary-general of the United Nations (UNSG or UNSECGEN) is the chief administrative officer of the United Nations and head of the United Nations Secretariat, one of the United Nations System#Six principal organs, six principal organs of ...

that methcathinone should be listed as a

in the

. In 1995, following US advice,

China China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...

added the drug to its list of prohibited substances and discontinued its pharmaceutical use. It is currently a Schedule III drug in Canada along with codeine, anabolic steroids, and testosterone. It is legal to possess in Canada, but illegal to purchase. Methcathinone used to have the nick-name "bath salts", to avoid restrictions on importation.

Chemistry

Methcathinone is a beta-keto ''N''-methylamphetamine and is closely related to the naturally occurring compounds,

and

cathine Cathine, also known as -norpseudoephedrine or as (+)-norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine groups which acts as a stimulant. Along with cathinone, it is found naturally in ''Catha edulis'' (khat), and ...

. It is also very closely related to

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 ...

, differing by only the β-

ketone In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...

substituent and differing from

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 both a keto and N-methyl substituent. Its carbon skeleton is identical to pseudoephedrine and methamphetamine. It differs from pseudoephedrine in that the hydroxyl beta to the aromatic ring is oxidized to a ketone. Methcathinone possesses a chiral carbon atom, and therefore ''two'' enantiomers are possible. When it is made semi-synthetically from pseudo/ephedrine as a starting material, then only a single enantiomer is produced. Given that the chiral center has an alpha hydrogen and adjacent the carbonyl group, the molecule will

racemize In chemistry, racemization is a conversion, by heat or by chemical reaction, of an optically active compound into a racemic (optically inactive) form. This creates a 1:1 molar ratio of enantiomers and is referred to as a racemic mixture (i.e. conta ...

in solution via an

enol In organic chemistry, enols are a type of functional group or intermediate in organic chemistry containing a group with the formula (R = many substituents). The term ''enol'' is an abbreviation of ''alkenol'', a portmanteau deriving from "-ene ...

intermediate. This process is known as

keto–enol tautomerism In organic chemistry, enols are a type of functional group or chemical intermediate, intermediate in organic chemistry containing a group with the formula (R = many substituents). The term ''enol'' is an abbreviation of ''alkenol'', a portmante ...

. Methcathinone production utilizes the

oxidation Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

pseudoephedrine Pseudoephedrine, sold under the brand name Sudafed among others, is a sympathomimetic medication which is used as a decongestant to treat nasal congestion. It has also been used off-label for certain other indications, like treatment of lo ...

ephedrine Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent hypotension, low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred ...

, the former being preferred because of much higher yields achieved. Oxidation of

to methcathinone requires little

chemistry Chemistry is the scientific study of the properties and behavior of matter. It is a physical science within the natural sciences that studies the chemical elements that make up matter and chemical compound, compounds made of atoms, molecules a ...

experience, making it (relatively) easy to synthesize.

Potassium permanganate Potassium permanganate is an inorganic compound with the chemical formula KMnO4. It is a purplish-black crystalline salt, which dissolves in water as K+ and ions to give an intensely pink to purple solution. Potassium permanganate is widely us ...

(KMnO₄) is most commonly used as the oxidant. In clandestine laboratories, synthesizing methcathinone using potassium permanganate is considered undesirable because of the low yields and the high toxicity of this oxidant ; however, if done in a proper laboratory using the proper procedures potassium permanganate can be a high-yielding reactant. A method that yields more methcathinone is oxidizing (pseudo)ephedrine with

chromium (VI) Hexavalent chromium (chromium(VI), Cr(VI), chromium 6) is any chemical compound that contains the element chromium in the +6 oxidation state (thus hexavalent). It has been identified as carcinogenic, which is of concern since approximately of ...

compounds, which are far more toxic than permanganate compounds. Methcathinone as free base is very unstable; it easily loses its

group, which is substituted with a

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

group, yielding

, in the reverse of the typical synthesis reaction. Structurally, this occurs when the C=O bond at the Rβ-position is converted into a C-OH bond. Additionally, a dimerization reaction has been observed in solutions of freebase methcathinone, which yields a biologically inactive compound.

Effects

Methcathinone hydrochloride increases spontaneous rodent locomotor activity, potentiates the release of

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 ...

from dopaminergic nerve terminals in the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

, and causes

appetite suppression An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...

. Users can easily forget to consume fluids leading to increased thirst and dehydration. The effects of methcathinone are similar to those of

, initially deemed to be less intense by the inexperienced user, and often more euphoric. The effects have been compared to those of

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

, since it commonly causes

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 ...

(elevated blood pressure) and

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 ...

(elevated heart rate). Reported effects include: * Feelings of

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 da ...

* Increased alertness * Slurred speech * Shaking of the limbs * Increased heart rate * Increased blood pressure, risk of stroke or heart attack * Increased empathy and sense of communication * Both decreased and increased sexual function and desire *

Bruxism Bruxism is excessive teeth grinding or jaw clenching. It is an oral Parafunctional habit, parafunctional activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; the global prevalence of brux ...

The effects of methcathinone usually last from four to six hours.

Pharmacology

Pharmacodynamics

Methcathinone is a

norepinephrine–dopamine releasing agent A norepinephrine–dopamine releasing agent (NDRA) is a type of drug which induces the synapse, release of norepinephrine (and epinephrine) and dopamine in the body and/or brain. Many of these are amphetamine type stimulants. Examples Examples ...

(NDRA). Methcathinone has very strong affinities for the

dopamine transporter The dopamine transporter (DAT, also sodium-dependent dopamine transporter) is a membrane-spanning protein coded for in humans by the ''SLC6A3'' gene (also known as ''DAT1''), that pumps the neurotransmitter dopamine out of the synaptic cleft ba ...

(DAT) and the

norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium ...

(NET). Its affinity for the

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein t ...

(SERT) is less than that of

. The C=O bond at the ''R_β''-position (directly right of the phenyl ring) is slightly polar, and as a result the drug does not cross the lipid

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

quite as well as

. Nevertheless, it is a potent central nervous system (CNS)

and

dopamine reuptake inhibitor A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dop ...

. Chronic high dosage use may result in acute mental confusion ranging from mild

paranoia Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety, suspicion, or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of co ...

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 ...

. These symptoms typically disappear quickly if use is stopped. Anecdotal reports have provided some information on patterns of methcathinone use. The most common

route of administration In pharmacology and toxicology, a route of administration is the way by which a medication, drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance ...

is via

nasal Nasal is an adjective referring to the nose, part of human or animal anatomy. It may also be shorthand for the following uses in combination: * With reference to the human nose: ** Nasal administration, a method of pharmaceutical drug delivery * ...

insufflation In religious and magical practice, insufflation and exsufflation are ritual acts of blowing, breathing, hissing, or puffing that signify variously expulsion or renunciation of evil or of the devil (the Evil One), or infilling or blessing with go ...

(snorting). Other routes of administration include ''

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

'', IV injection and

smoking Smoking is a practice in which a substance is combusted, and the resulting smoke is typically inhaled to be tasted and absorbed into the bloodstream of a person. Most commonly, the substance used is the dried leaves of the tobacco plant, whi ...

Illicit usage

Methcathinone binges resemble amphetamine binges in that the user may not sleep or eat, and takes in little in the way of liquids. The methcathinone binge is followed by long periods of sleep, excess eating, long-lasting nosebleeds (

of methcathinone is corrosive to the

nasal mucosa The nasal mucosa lines the nasal cavity. It is part of the respiratory mucosa, the mucous membrane lining the respiratory tract. The nasal mucosa is intimately adherent to the periosteum or perichondrium of the nasal conchae. It is continuous w ...

in the same manner as methamphetamine) and, in some cases, depression.

Addiction

In preclinical studies, methcathinone

hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternati ...

produces an abuse potential similar to that of the

amphetamines Substituted amphetamines, or simply amphetamines, are a chemical class, class of compounds based upon the amphetamine structure; it includes all derivative (chemistry), derivative compounds which are formed by replacing, or substitution reacti ...

. Methcathinone can be highly psychologically addictive, and can produce a

-like withdrawal. In drug discrimination studies, methcathinone hydrochloride evokes responses similar to those induced by both dextroamphetamine sulfate and

hydrochloride.

Intravenous usage

Injecting this substance has been associated with symptoms similar to those seen in patients with

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

(

manganism Manganism or manganese poisoning is a toxic condition resulting from chronic exposure to manganese. It was first identified in 1837 by James Couper. Signs and symptoms Chronic exposure to excessive manganese levels can lead to a variety of psyc ...

) due to the compound

manganese dioxide Manganese dioxide is the inorganic compound with the formula . This blackish or brown solid occurs naturally as the mineral pyrolusite, which is the main ore of manganese and a component of manganese nodules. The principal use for is for dry-cel ...

which is a byproduct of synthesis with

permanganate A permanganate () is a chemical compound with the manganate(VII) ion, , the conjugate base of permanganic acid. Because the manganese atom has a +7 oxidation state, the permanganate(VII) ion is a strong oxidising agent. The ion is a transition ...

Legal status

The

lists methcathinone as a Schedule I substance which restricts its use for government-approved medical and scientific uses.

Australia

Methcathinone is a Schedule 9 prohibited substance in

Australia Australia, officially the Commonwealth of Australia, is a country comprising mainland Australia, the mainland of the Australia (continent), Australian continent, the island of Tasmania and list of islands of Australia, numerous smaller isl ...

under the Poisons Standard (February 2021). A Schedule 9 substance is defined as a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.

United Kingdom

In the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...

, methcathinone is listed as a Class B drug with no clinical uses.

United States

In the

, methcathinone is listed as a Schedule I drug, for which there is no clinical use.

Netherlands

In the

Netherlands , Terminology of the Low Countries, informally Holland, is a country in Northwestern Europe, with Caribbean Netherlands, overseas territories in the Caribbean. It is the largest of the four constituent countries of the Kingdom of the Nether ...

, methcathinone is listed as a Level I substance of the

Opium Law The Opium Law (''Opiumwet'' in Dutch) is the section of the Dutch law which covers nearly all psychotropic drugs. Origin and history In 1912, the First International Opium Conference took place in The Hague, where agreements were made about ...

, for which there is no clinical use.

References

External links

Cathinone & Methcathinone from Erowid

International Drug Scheduling; Convention on Psychotropic Substances; Certain Stimulant/Hallucinogenic Drugs and Certain Nonbarbiturate Sedative Drugs
Food and Drug Administration, June 20, 1994.
Methcathinone from lycaeum
{{Chemical classes of psychoactive drugs Cathinones Euphoriants Methamphetamines Monoaminergic neurotoxins Norepinephrine-dopamine releasing agents Stimulants

History

Chemistry

Effects

Pharmacology

Pharmacodynamics

Illicit usage

Addiction

Intravenous usage

Legal status

Australia

United Kingdom

United States

Netherlands

See also

References

External links