IsoDMT

isoDMT, also known as N,''N''-dimethylisotryptamine, is a putatively non-hallucinogenic serotonin 5-HT_2A receptor agonist and psychoplastogen of the isotryptamine group. It is the isotryptamine homologue of dimethyltryptamine, a more well-known serotonergic psychedelic of the tryptamine family, and represents a small structural modification of DMT.

Pharmacology

Pharmacodynamics

isoDMT does not produce hallucinogen-like stimulus generalization in animal drug discrimination tests and similarly does not produce the head-twitch response, 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 psychoplastogenic effects comparable to those of serotonergic psychedelics in preclinical research. Its affinities for the serotonin 5-HT₂ receptors have been reported to be 600–650nM for 5-HT_2A and 720nM at 5-HT_2C.

Chemistry

Analogues

Several derivatives of isoDMT have been developed, including the non-hallucinogenic psychoplastogens 5-MeO-isoDMT and zalsupindole and the hallucinogen and psychoplastogen 6-MeO-isoDMT. Zalsupindole has shown antidepressant-like effects in animals, thought to be secondary to its psychoplastogenic actions, and is under development for potential medical use to treat neuropsychiatric disorders like depression. Another analogue of isoDMT is α-methylisotryptamine, the isotryptamine homologue of α-methyltryptamine.

History

isoDMT and its derivatives were first described in the scientific literature by 1984. They were subsequently further characterized in 2020.