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 . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ...

amino In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...

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 ar ...

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of simila ...

and

psychoactive 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. Th ...

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 ...

, a substituted

cathinone Cathinone (also known as benzoylethanamine, or β-keto-amphetamine) 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 mai ...

. It is used as a

recreational drug Recreational drug use indicates 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 by modifying the perceptions and emotions of the user. When a ...

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 da ...

effects and is considered to be

addictive Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use oft ...

, 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 This is the list of Schedule I drugs as defined by the United States Controlled Substances Act. 21 CFRbr>1308.11(CSA Sched I) with changes through (Oct 18, 2012). Retrieved September 6, 2013. The following findings are required for drugs to be pla ...

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 (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

Controlled Substances Act 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 States ...

, 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 19 ...

in 1957. It was used in the

Soviet Union The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, it was nominally a federal union of fifteen nationa ...

during the 1930s and 1940s as an

anti-depressant 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, heada ...

(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 transcontinental country spanning Eastern Europe and Northern Asia. It is the largest country in the world, with its internationally recognised territory covering , and encompassing one-ei ...

. Circa 1994, the United States government recommended to the

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

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. It is the world's List of countries and dependencies by population, most populous country, with a Population of China, population exceeding 1.4 billion, slig ...

added the drug to its list of prohibited substances and discontinued its pharmaceutical use.

Chemistry

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

and

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

. 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 and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamp ...

, differing by only the β-

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double b ...

substituent and differing from

amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

by both a keto and N-methyl substituent. Its carbon skeleton is identical to pseudoephedrine and methamphetamine. It differs from pseudoephedrine in that the hydroxide 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 In the nomenclature of organic chemistry, a locant is a term to indicate the position of a functional group or substituent within a molecule. Numeric locants The International Union of Pure and Applied Chemistry (IUPAC) recommends the use of n ...

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 too as a racemic mixture (i.e. conta ...

in solution via an

enol In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). T ...

intermediate. This process is known as keto–enol tautomerism. Methcathinone production utilizes the

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

pseudoephedrine Pseudoephedrine (PSE) is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent in higher doses. It was first charact ...

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

, 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 natural science that covers the elements that make up matter to the compounds made of atoms, molecules and ions: their composition, structure, proper ...

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, that dissolves in water as K+ and , an intensely pink to purple solution. Potassium permanganate is widely used in the c ...

(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 chromium in any chemical compound that contains the element in the +6 oxidation state (thus hexavalent). Virtually all chromium ore is processed via hexavalent chromium, specifically the s ...

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 hydrox ...

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. Dopamine constitutes about 80% o ...

from dopaminergic nerve terminals in the

brain A brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as Visual perception, vision. I ...

, and causes appetite suppression. 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 (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...

, since it commonly causes

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...

(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 d ...

* 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 activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; reports of prevalence range from 8% to 31% in the gen ...

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

Pharmacology

Methcathinone has very strong affinities for the dopamine transporter and the norepinephrine (noradrenaline) transporter. Its affinity for the serotonin transporter is less than that of methamphetamine. 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 border of endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where ne ...

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 ...

. 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 or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy c ...

psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavi ...

. 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 A route of administration in pharmacology and toxicology is the way by which a 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 applied. ...

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 ''

per os Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

'', IV injection and

smoking Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have b ...

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 ...

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 alternative n ...

produces an abuse potential similar to that of the

amphetamines Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with sub ...

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

-like withdrawal, which is somewhat lower in intensity than

. In

drug discrimination studies 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 insuffla ...

, methcathinone hydrochloride evokes responses similar to those induced by both dextroamphetamine sulfate and

hydrochloride. While both the

dextrorotary Optical rotation, also known as polarization rotation or circular birefringence, is the rotation of the orientation of the plane of polarization about the optical axis of linearly polarized light as it travels through certain materials. Circul ...

and levorotary enantiomeric forms of methcathinone hydrochloride have been found to be pharmacologically active when examined in particular pharmacological assays for psychomotor

-like activity, the levorotary form of methcathinone is more active than the dextrorotary forms of both methcathinone and notable, as it is the dextrorotary isomer that is more active both for amphetamine and methamphetamine. Some street dealers are selling methcathinone as dextroamphetamine or methamphetamine but the drug is more dangerous to people who inject it than the more common amphetamine.

Intravenous usage

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

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...

(

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-ce ...

which is a byproduct of synthesis with

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

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 sovereign country comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands. With an area of , Australia is the largest country by ...

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 Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and ...

, 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 ) , anthem = ( en, "William of Nassau") , image_map = , map_caption = , subdivision_type = Sovereign state , subdivision_name = Kingdom of the Netherlands , established_title = Before independence , established_date = Spanish Netherl ...

, methcathinone is listed as a Level I substance of the

Opium Law The Opium Law (or ''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 abou ...

, 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
{{Phenethylamines Cathinones Euphoriants Norepinephrine-dopamine releasing agents Stimulants Substituted amphetamines

History

Chemistry

Effects

Pharmacology

Illicit usage

Addiction

Intravenous usage

Legal status

Australia

United Kingdom

United States

Netherlands

See also

References

External links