α-Methylisotryptamine (isoAMT or α-Me-isoT) is a synthetic compound belonging to the

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

class, known for its psychoactive properties. As a structural analog of α-methyltryptamine (αMT), isoAMT exhibits entactogenic and

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 ...

effects.

Pharmacology

α-Methylisotryptamine 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 ...

and

serotonin receptor agonist A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin (5-hydroxytryptamine; 5-HT), a neurotransmitter and hormone and the endogenous ligand of t ...

of the

isotryptamine Isotryptamine, also known as 2-(1-indolyl)ethylamine, is a chemical compound and positional isomer of tryptamine (2-(3-indolyl)ethylamine). A variety of isotryptamine chemical derivative, derivatives, or chemical substituent, substituted isotrypt ...

group. It is the isotryptamine homologue of α-methyltryptamine (αMT), which is a more well-known

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 ...

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 ...

, and

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, ...

of the

family with similar

pharmacological Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between ...

actions. Like αMT, α-methylisotryptamine is a

. As the (–)-

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

, it specifically acts as a preferential serotonin and norepinephrine releasing agent (SNRA), with values of 177nM 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, ...

release, 81nM 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 ...

release, and 1,062nM for

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. In contrast to

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 ...

and similar agents acting as potent and selective dopamine and norepinephrine releasing agents, (–)-α-methylisotryptamine showed no misuse potential in

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 ...

, including no

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

-like effects in

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 and no facilitation of

intracranial self-stimulation Brain stimulation reward (BSR) is a pleasurable phenomenon elicited via direct stimulation of specific brain regions, originally discovered by James Olds and Peter Milner. BSR can serve as a robust operant reinforcer. Targeted stimulation activ ...

(ICSS). In addition to its monoamine release, α-methylisotryptamine 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 5-HT₂ receptors.

Analogs

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

of α-methylisotryptamine,

zalsupindole Zalsupindole,https://iris.who.int/bitstream/handle/10665/380497/9789240107038-eng.pdf "zalsupindolum zalsupindole (2R)-1-(5-methoxy-1H-indol-1-yl)-N,N-dimethylpropan-2-amine antidepressant" also known by its developmental code names DLX-001 and ...

(DLX-001; AAZ-A-154; (''R'')-5-MeO-''N'',''N''-dimethyl-isoAMT), is a non-

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 serotonin 5-HT_2A receptor

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 ...

and is being developed for potential medical use in the treatment depression and other

neuropsychiatric disorder A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...

s. Other derivatives of α-methylisotryptamine have also been developed, such as the selective serotonin 5-HT_2C receptor agonists (''S'')-5,6-difluoro-isoAMT and

Ro60-0175 Ro60-0175, also known as (''S'')-5,6-difluoroindolmethylethylamine, is a serotonin receptor agonist of the isotryptamine group developed by Hoffmann–La Roche, which has applications in scientific research. It acts as a potent and selective ...

((''S'')-5-fluoro-6-chloro-isoAMT), among others.

References

{{DEFAULTSORT:Methylisotryptamine, alpha- Isotryptamines Serotonin-norepinephrine releasing agents Serotonin receptor agonists

Pharmacology

Analogs

See also

References