2,4,6-Trimethoxyamphetamine (2,4,6-TMA), also known as TMA-6 or ψ-TMA-2, 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

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 of

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).

Use and effects

In his 1991 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 ...

'' (''Phenethylamines I Have Known and Loved''),

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 ...

gave a dose range for TMA-6 of 25 to 50mg and a duration of 12 to 16hours. Threshold effects occur at 20mg, a full

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 state occurs at 30 to 40mg, and erratic results have been reported for 40 to 80mg. The drug is said to have about 8 to 10times the

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 ...

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 ...

. Its effects at 25 to 50mg included ease with concepts and writing, body tingling, walking unsteadiness, thinking difficulty or

intoxication Intoxication — or poisoning, especially by an alcoholic or narcotic substance — may refer to: * Substance intoxication: ** Alcohol intoxication ** LSD intoxication ** Toxidrome ** Tobacco intoxication ** Cannabis intoxication ** Cocaine i ...

, difficulty with tasks, funniness, hilarity, and laughter,

difficulty sleeping Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

, inner chill, visual sparkle, stomach queasiness,

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

, reduced appetite, fluctuating emotions, personal insights,

visual The visual system is the physiological basis of visual perception (the ability to detect and process light). The system detects, transduces and interprets information concerning light within the visible range to construct an image and buil ...

s, colors, and feelings of "energy flow". Additional reported effects include enjoyable

lightheadedness Lightheadedness is a common and typically unpleasant sensation of dizziness or a feeling that one may faint. The sensation of lightheadedness can be short-lived, prolonged, or, rarely, recurring. In addition to dizziness, the individual may fee ...

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 ...

, perceptual distortion,

synesthesia Synesthesia (American English) or synaesthesia (British English) is a perceptual phenomenon in which stimulation of one sensory or cognitive pathway leads to involuntary experiences in a second sensory or cognitive pathway. People with sy ...

, and

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

Interactions

Pharmacology

Pharmacodynamics

TMA-6 shows

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 ...

for

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

s in rat stomach fundus strips (A₂ = 525nM) as well as in rat brain membranes ( = 25,000nM). In a later study, it showed no affinity for the

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_1A or

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 ...

D₂ receptors (K_i = >10,000nM). It was inactive as a

monoamine reuptake inhibitor A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamin ...

and

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 ...

in rat brain

synaptosome A synaptosome is an isolated synaptic terminal from a neuron. Synaptosomes are obtained by mild homogenization of nervous tissue under isotonic conditions and subsequent fractionation using differential and density gradient centrifugation. Liquid ...

s ( and = >100,000nM, respectively). The drug is a potent

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)

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

, with an of 400nM. This is in contrast to TMA (3,4,5-TMA) and TMA-2 (2,4,5-TMA), which are inactive in this regard. TMA-6 fully substitutes for the

s DOM and

5-MeO-DMT 5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine), also known as ''O''-methylbufotenin or mebufotenin (), is a naturally occurring psychedelic of the tryptamine family. It is found in a wide variety of plant species, and is also secreted by ...

in rodent

drug discrimination Drug discrimination (DD) is a technique in behavioral neuroscience used to evaluate the discriminative stimulus properties or interoceptive cues of psychoactive drugs. In drug discrimination, a subject is trained on a training drug, and then i ...

tests. It also partially substitutes for

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 ...

in rodent drug discrimination tests.

Chemistry

Analogues

A number of analogues of TMA-6 with a 2,4,6- substitution pattern have been described, such as Ψ-DOM and

ψ-2C-T-4 2C-T-4, also known as 4-isopropylthio-2,5-dimethoxyphenethylamine, is a psychedelic phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin and is used as entheogenic recreational drug. Effects 2C-T-4 produces psychedelic ...

, among others.

only limitedly explored the 2,4,6- substitution pattern.

History

TMA-6 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 ...

by 1954.

discovered its psychedelic effects in 1964 and first described its hallucinogenic effects in the literature in 1969, where he stated its potency relative to mescaline and noted that these findings were previously unpublished. Shulgin subsequently gave the drug the name ''TMA-6'' in 1970. He more thoroughly described TMA-6 in ''PiHKAL'' in 1991. The drug was encountered as a novel

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. ...

Europe Europe is a continent located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south, and Asia to the east ...

in 2009.

Society and culture

Legal status

As a

of TMA, TMA-6 is said to be 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 ...

References

External links

TMA-6 - Isomer Design

TMA-6 - PsychonautWiki
{{DEFAULTSORT:Trimethoxyamphetamine, 2,4,6- Methoxyphenethylamines Monoamine oxidase inhibitors Psychedelic phenethylamines Serotonin receptor modulators Substituted amphetamines