Methiopropamine (MPA), also known as ''N''-methylthiopropamine, is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

structurally 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 ...

. Originally reported in 1942, the molecule consists of a

thiophene Thiophene is a heterocyclic compound with the formula C4H4S. Consisting of a planar five-membered ring, it is aromatic as indicated by its extensive substitution reactions. It is a colorless liquid with a benzene-like odor. In most of its reacti ...

group A group is a number of persons or things that are located, gathered, or classed together. Groups of people * Cultural group, a group whose members share the same cultural identity * Ethnic group, a group whose members share the same ethnic iden ...

with an

alkyl In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl group is derived from a cy ...

amine 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 ...

substituent In organic chemistry, a substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. The suffix ''-yl'' is used when naming organic compounds that contain a single bond r ...

at the 2-position. It appeared for public sale 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 ...

in December 2010 as a "research chemical" or "legal high", recently branded as Blow. It has limited popularity as a

recreational Recreation is an activity of leisure, leisure being discretionary time. The "need to do something for recreation" is an essential element of human biology and psychology. Recreational activities are often done for enjoyment, amusement, or plea ...

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, ...

Pharmacology

Methiopropamine functions as a

norepinephrine–dopamine reuptake inhibitor A norepinephrine–dopamine reuptake inhibitor (NDRI) is a type of drug that inhibits the reuptake of the monoamine neurotransmitters norepinephrine and dopamine and thereby increases extracellular levels of these neurotransmitters and nor ...

(NDRI) that is approximately 1.85 times more selective for

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 ...

than

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 ...

. It is approximately one-third as potent as

dextroamphetamine Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...

as a

norepinephrine reuptake inhibitor A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinep ...

and one-fifth as much as a

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 ...

. It displays negligible activity as a

serotonin reuptake inhibitor A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the drug action, action of the serotonin transporter (SERT). This in turn lea ...

. Methiopropamine has the potential for significant

acute toxicity Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours). To be described as ''acute'' toxicity, the adverse effect ...

with

cardiovascular In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart a ...

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

, and

psychotic 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 incoher ...

symptoms.

Metabolism

For ''N''-alkyl amphetamines,

deamination Deamination is the removal of an amino group from a molecule. Enzymes that catalysis, catalyse this reaction are called deaminases. In the human body, deamination takes place primarily in the liver; however, it can also occur in the kidney. In s ...

and ''N''-

dealkylation Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...

are the major elimination pathways and

renal In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retrop ...

excretion Excretion is elimination of metabolic waste, which is an essential process in all organisms. In vertebrates, this is primarily carried out by the lungs, Kidney (vertebrates), kidneys, and skin. This is in contrast with secretion, where the substa ...

is a minor one. Methiopropamine 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 ...

into active

thiopropamine Thiopropamine, also known as 1-(2-thienyl)-2-aminopropane, is a stimulant drug of the arylalkylamine family. It is an analogue of amphetamine where the phenyl ring has been replaced by thiophene. It has similar stimulant effects to amphetamine b ...

, 4-hydroxymethiopropamine and

''S''-

oxide An oxide () is a chemical compound containing at least one oxygen atom and one other element in its chemical formula. "Oxide" itself is the dianion (anion bearing a net charge of −2) of oxygen, an O2− ion with oxygen in the oxidation st ...

s. These ''N''-

demethylated Demethylation is the chemical process resulting in the removal of a methyl group (CH3) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen at ...

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 further deaminated by the

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzyme

CYP2C19 Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some ...

in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

transforming them into inactive 1-(thiophen-2-yl)-2-propan-2-one which can be seen as a

phenylacetone Phenylacetone, also known as phenyl-2-propanone, is an organic compound with the chemical formula C6H5CH2COCH3. It is a colorless oil that is soluble in organic solvents. It is a mono- substituted benzene derivative, consisting of an acetone att ...

derivative. Thiophene-2-carboxylic acid is the final major metabolic product. It is very

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...

and is excreted in urine. Methiopropamine and especially

are also excreted

ly, unchanged.

Synthesis

There is a four-step synthesis of methiopropamine. It begins with (thiophen-2-yl)magnesium bromide, which is reacted with

propylene oxide Propylene oxide is an epoxide with the molecular formula C3H6O. This colourless volatile liquid with an odour similar to ether, is produced on a large scale industrially. Its major application is its use for the production of polyether polyols f ...

, yielding 1-(thiophen-2-yl)-2-hydroxypropane which is reacted with

phosphorus tribromide Phosphorus tribromide is a colourless liquid with the formula P Br3. The liquid fumes in moist air due to hydrolysis and has a penetrating odour. It is used in the laboratory for the conversion of alcohols to alkyl bromides. Preparation PBr3 ...

, yielding 1-(thiophen-2-yl)-2-bromopropane which is finally reacted with

methylamine Methylamine, also known as methanamine, is an organic compound with a formula of . This colorless gas is a derivative of ammonia, but with one hydrogen atom being replaced by a methyl group. It is the simplest primary amine. Methylamine is sold ...

, yielding 1-(thiophen-2-yl)-2-methylaminopropane. Methiopropamine synthesis

Legal status

China

As of October 2015 MPA is a controlled substance in China.

Finland

Methiopropamine is illegal in

Finland Finland, officially the Republic of Finland, is a Nordic country in Northern Europe. It borders Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of Bothnia to the west and the Gulf of Finland to the south, ...

, it is scheduled in "government decree on narcotic substances, preparations and plants".

Germany

Methiopropamine is explicitly illegal in Germany.

United Kingdom

Following the ban on

ethylphenidate Ethylphenidate (EPH) is a central nervous system (CNS) stimulant and a close analog of methylphenidate. Ethylphenidate acts as a norepinephrine–dopamine reuptake inhibitor, meaning it effectively boosts the levels of the norepinephrine and do ...

, authorities noticed an increase in methiopropamine use by injecting users. The ACMD suggested it be banned on 18 November 2015 as it had similar effects to ethylphenidate. The government enacted a temporary drug control order a week later which came into force on 27 November 2015. Though ordinarily the TCDO would only last 1 year, the ACMD reported that since its invocation prevalence of MPA had significantly decreased, and that it had been challenging to collect information about the drug. As a result of this, they requested that the TCDO be extended a further year. Methiopropanine was made a Class B controlled drug under the Misuse of Drugs Act 1971 (as amended) (Amendment)(No.2) Order 2017 I 2017/1114 this came into effect on the 27th of November 2017.

United States

Methiopropamine is scheduled at the federal level in 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 ...

. The DEA had planned to place methiopropamine in Schedule I of Controlled Substances and was accepting public comments until October 4, 2021. Later, the compound was placed in Schedule I.

Florida

Methiopropamine is a Schedule I

controlled substance 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 Sing ...

in the state of

Florida Florida ( ; ) is a U.S. state, state in the Southeastern United States, Southeastern region of the United States. It borders the Gulf of Mexico to the west, Alabama to the northwest, Georgia (U.S. state), Georgia to the north, the Atlantic ...

making it illegal to buy, sell, or possess in Florida.Florida Statutes - Chapter 893 - DRUG ABUSE PREVENTION AND CONTROL
/ref>

Tasmania (Australia)

Methiopropamine is a "controlled substance" and therefore an "illegal drug" to import, possess or sell/traffic in without express authority of the relevant government agency.

References

External links

Methiopropamine
at erowid.org
Methiopropamine
at isomerdesign.com
Methiopropamine
at psychonautwiki.org {{Stimulants Secondary amines Designer drugs Norepinephrine–dopamine reuptake inhibitors Stimulants Thiopropamines