3,4,5-Trimethoxyamphetamine (TMA, TMA-1, or 3,4,5-TMA), also known as α-methylmescaline or mescalamphetamine, is a

psychedelic drug Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluc ...

of the

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

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 ...

families. It is one of the

trimethoxyamphetamine 3,4,5-Trimethoxyamphetamine (TMA, TMA-1, or 3,4,5-TMA), also known as α-methylmescaline or mescalamphetamine, is a psychedelic drug of the phenethylamine and amphetamine families. It is one of the trimethoxyamphetamine (TMA) series of positiona ...

(TMA) series of

positional isomer In chemistry, a structural isomer (or constitutional isomer in the IUPAC nomenclature) of a compound is a compound that contains the same number and type of atoms, but with a different connectivity (i.e. arrangement of bonds) between them. The ...

s. The drug is notable in being the amphetamine (i.e., α-

methylated Methylation, in the chemical sciences, is the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These term ...

) analogue of

mescaline Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a natural product, naturally occurring psychedelic drug, psychedelic alkaloid, protoalkaloid of the substituted phenethylamine class, found ...

(3,4,5-trimethoxyphenethylamine).

Use and effects

TMA is a

serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

and produces

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

ic effects. It is said to be active at doses of 100 to 250mg and to have a duration of 6 to 8hours. For comparison,

is typically used at doses of 200 to 500mg and is said to have a duration of 10 to 12hours or longer. TMA's positional isomer 2,4,5-trimethoxyamphetamine (2,4,5-TMA or TMA-2) is much more potent than TMA, with a dosage of 20 to 40mg and a duration of 8 to 12hours.

Interactions

Pharmacology

TMA is a low-

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of ho ...

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, ...

5-HT_2A receptor

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

, with an

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

(K_i) of >12,000nM, an of 1,700nM, and an of 40%. Conversely, it was inactive at the serotonin 5-HT_1A, 5-HT_2B and 5-HT_2C receptors and at several other receptors, at least at the assessed concentrations (up to 10,000nM). It showed affinity for the mouse and rat

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) (K_i = 1,800nM and 3,200nM, respectively), whereas it was inactive at the human TAAR1 ( > 10,000nM). TMA is also a very low-potency

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 ...

(SRA), with an value of 16,000nM. In contrast, it is inactive 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 ...

and

reuptake inhibitor Reuptake inhibitors (RIs) are a type of reuptake modulators. It is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracel ...

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 ...

and

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 ...

( > 100,000nM). Despite its apparent SRA activity ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'', TMA did not increase brain serotonin or dopamine levels in rodents ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

''. TMA is similarly inactive as a

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), including of both

monoamine oxidase 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 dea ...

(MAO-A) and

monoamine oxidase 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 catalyzes ...

(MAO-B) ( > 200,000nM). The low potency of TMA as a serotonin 5-HT_2A receptor agonist is analogous to the case of mescaline, which is a well-known and widely used psychedelic but is likewise a very low-potency agonist of this receptor, showing an affinity (K_i) of 9,400nM, an of 10,000nM, and an of 56% in the same study. For comparison, DOM has shown an affinity (K_i) of 88nM and an of 4 to 24nM.

History

TMA was first synthesized by

Gordon Alles Gordon A. Alles (November 26, 1901 – January 21, 1963), was an American chemist and pharmacologist who did extensive research on the isolation and properties of insulin for the treatment of diabetes, diabetics. He is also credited with discoveri ...

around 1937. He assessed it in both

animal studies Animal studies is a recently recognised field in which animals are studied in a variety of cross-disciplinary ways. Scholars who engage in animal studies may be formally trained in a number of diverse fields, including art history, anthropology ...

and

self-experiment Self-experimentation refers to single-subject research in which the experimenter conducts the experiment on themself. Usually this means that a single person is the designer, operator, subject, analyst, and user or reporter of the experiment. Al ...

s and documented its effects, but these were not reported until 1959. The drug was first described in the

scientific literature Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ...

in 1947 and its psychedelic effects were first described in 1955. TMA was studied at

Edgewood Arsenal Aberdeen Proving Ground (APG) is a U.S. Army facility located adjacent to Aberdeen, Harford County, Maryland, United States. More than 7,500 civilians and 5,000 military personnel work at APG. There are 11 major commands among the tenant units, ...

under the code name EA‐1319 in 1953 and 1954. The drug was further characterized by

Alexander Shulgin Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014) was an American biochemist, broad researcher of synthetic psychoactive compounds, and author of works regarding these, who independently explored the organic chemistry and ph ...

and described in his book ''

PiHKAL ''PiHKAL: A Chemical Love Story'' is a book by Alexander Shulgin and Ann Shulgin published in 1991. The subject of the work is Psychoactive drug, psychoactive phenethylamine Derivative (chemistry), chemical derivatives, notably those that act ...

''.

Society and culture

Legal status

TMA 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

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 ...

.https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf

References

External links

TMA - Isomer Design

TMA - PiHKAL - Erowid

TMA - PiHKAL - Isomer Design
{{DEFAULTSORT:Trimethoxyamphetamine, 3,4,5- 3C (psychedelics) 5-HT2A agonists 5-HT2C agonists Alexander Shulgin Methoxy compounds Nicotinic acetylcholine receptor modulators Psychedelic phenethylamines Serotonin receptor agonists Serotonin releasing agents Sigma receptor modulators Substituted amphetamines TAAR1 modulators