The Emergence of Isotryptamine Analogs as Novel Serotonergic Agents with Psychotherapeutic Potential (2026)

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https://doi.org/10.1021/acsptsci.6c00288

Glennon reviews the isotryptamines...

Abstract Isotryptamines, or 2-(1-indolyl)ethylamines, are positional or geometric isomers of tryptamines where the aminoethyl substituent has been relocated from the indole 3-position to the N1-position. Early studies with these types of agents relied on peripheral tissue assays for examination of their serotonin (5-hydroxytryptamine; 5-HT) receptor affinities to investigate structure–affinity relationships. Once 5-HT receptors were identified in the brain and as the binding methodology improved, isotryptamines were further examined, including various in vitro and in vivo assays (i.e., model systems) as techniques evolved. Given that certain hallucinogenic/psychedelic tryptamines, such as analogs of N,N-dimethyltryptamine (DMT), are currently of interest in the treatment of various neuropsychiatric disorders, there is renewed interest in agents such as isoDMT, and an isoDMT analog has now entered clinical trials. The history of isotryptamine analogs, from their discovery to the present, is reviewed.

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