4,4'-Dimethylaminorex (abbreviated as 4,4'-DMAR), sometimes referred to by the

street name A street name is an identifying name given to a street or road. In toponymic terminology, names of streets and roads are referred to as odonyms or hodonyms (from Ancient Greek 'road', and 'name', i.e., the Doric Greek, Doric and Aeolic Gre ...

"Serotoni", is a

psychostimulant 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 ...

and

entactogen Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is, empathy—as particularly observe ...

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

related to

aminorex Aminorex, sold under the brand names Menocil and Apiquel among others, is a weight loss (anorectic) stimulant drug. It was withdrawn from the market after it was found to cause pulmonary hypertension (PPH). In the United States, aminorex is a ...

4-methylaminorex 4-Methylaminorex (4-MAR, 4-MAX) is a stimulant drug of the 2-amino-5-aryloxazoline group that was first synthesized in 1960 by McNeil Laboratories. It is also known by its street name "U4Euh" ("Euphoria"). It is banned in many countries as a sti ...

, and

pemoline Pemoline, formerly sold under the brand name Cylert among others, is a stimulant medication which was used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy,- it has since been discontinued in most countries due ...

. It was first detected in the Netherlands in December 2012, and has been sold as a

around Europe since mid-2013. 4,4'-DMAR had been linked to at least 31 deaths in Hungary, Poland, and the UK by February 2014, mostly when consumed in combination with other drugs. Nineteen deaths linked to 4,4'-DMAR were reported in Northern Ireland in the same time period.

Pharmacology

Pharmacodynamics

4,4'-DMAR is a

monoamine 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 ...

(MRA) and acts specifically as a highly potent and well-balanced serotonin-norepinephrine-dopamine releasing agent (SNDRA), with EC₅₀ values for

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, ...

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 ...

, 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 ...

release Release may refer to: * Art release, the public distribution of an artistic production, such as a film, album, or song * Legal release, a legal instrument * News release, a communication directed at the news media * Release (ISUP), a code to i ...

of 18.5nM, 26.9nM, and 8.6nM, respectively. It also interacts with the

vesicular monoamine transporter 2 The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. VMAT2 is an integral membrane protein that transports monoamines—particul ...

(VMAT2) with similar potency as

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

. In contrast to many other MRAs, 4,4'-DMAR is inactive as a

trace amine-associated receptor 1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is a primarily intracellular amine-activated and G protein-coupled receptor (GPCR) that is p ...

(TAAR1)

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 ...

. As a result, whereas many other MRAs may auto-inhibit and constrain their effects via TAAR1 agonism, this may not occur with 4,4'-DMAR. The drug also shows very weak interactions with the serotonin 5-HT_2A and 5-HT_2C receptors, though appears to be inactive at the serotonin 5-HT_2B receptor.

Legality

The UK Home Office expressed intent to ban 4,4'-DMAR following advice from the

Advisory Council on the Misuse of Drugs The Advisory Council on the Misuse of Drugs (ACMD) is a British statutory advisory non-departmental public body, which was established under the Misuse of Drugs Act 1971. Mandate Its terms of reference, according to the Act, are as follows: ...

and subsequently it became a class A drug on 11 March 2015. 4,4'-DMAR is an

Anlage II The following drugs are controlled by the German Narcotic Drugs Act ( or ). Trade and drug possession, possession of these substances without licence or prescription is considered illegal; prescription is illegal for drugs on ''Anlage I'' and II an ...

controlled substance in Germany . Sweden's public health agency suggested to classify 4,4'-DMAR as hazardous substance on November 10, 2014. 4,4'-DMAR is also banned in the Czech Republic. 4,4'-DMAR is a Schedule I controlled substance in the US as of November 8, 2021. It only received two public comments during its public commenting period prior to being scheduled.

References

{{DEFAULTSORT:Dimethylaminorex, 4, 4'- Aminorexes Beta-Hydroxyamphetamines Designer drugs Entactogens Serotonin-norepinephrine-dopamine releasing agents Stimulants VMAT inhibitors

Pharmacology

Pharmacodynamics

Legality

See also

References