isoDMT, also known as ''N'',''N''-dimethylisotryptamine, is a putatively 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 ...

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

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

psychoplastogen Psychoplastogens, also known as neuroplastogens, are a group of Small molecule#Drugs, small molecule drugs that produce rapid and sustained effects on neuronal structure and function, intended to manifest therapeutic benefit after a single admin ...

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

dimethyltryptamine Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a Psychedelic drug, serotonergic hallucinogen and Investigational New Drug, investigational drug of the substituted tryptamine, tryptamine family tha ...

(DMT), 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 ...

of 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 ...

family, and represents a small structural modification of DMT.

Pharmacology

The drug does not produce hallucinogen-like stimulus generalization in animal

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 similarly does not produce the

head-twitch response The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats in association with serotonin 5-HT2A receptor activation. Serotonergic psychedelics like lys ...

, an animal behavioral proxy of psychedelic-like effects. As such, it is not expected to be hallucinogenic in humans. However, isoDMT retains significant activity at the serotonin 5-HT₂ receptors and shows

ic effects comparable to those of serotonergic psychedelics in

preclinical research In drug development, preclinical development (also termed preclinical studies or nonclinical studies) is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and dr ...

. Its affinities (K_i) for the serotonin 5-HT₂ receptors have been reported to be 600–650nM for 5-HT_2A and 720nM at 5-HT_2C.

Analogs

Several

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 ...

s of isoDMT have been developed, including the non-hallucinogenic psychoplastogens 5-MeO-isoDMT and zalsupindole (DLX-001; AAZ-A-154; (''R'')-5-MeO-α-methyl-isoDMT) and the hallucinogen and psychoplastogen 6-MeO-isoDMT. Zalsupindole has shown

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

-like effects in animals, thought to be secondary to its psychoplastogenic actions, and is under development for potential medical use to treat

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 like depression. Another analogue of isoDMT is

α-methylisotryptamine α-Methylisotryptamine (isoAMT or α-Me-isoT) is a synthetic compound belonging to the tryptamine class, known for its psychoactive properties. As a structural analog of α-methyltryptamine (αMT), isoAMT exhibits entactogenic and psychedelic e ...

(isoAMT), the isotryptamine homologue of α-methyltryptamine (AMT).

History

isoDMT and its derivatives were 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 1984. They were subsequently further characterized in 2020.

References

{{Tryptamines Dimethylamino compounds Isotryptamines Non-hallucinogenic 5-HT2A receptor agonists Serotonin receptor agonists

Pharmacology

Analogs

History

See also

References