1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents - A Review.
Richard A Glennon, Małgorzata Dukat
ACS Pharmacology & Translational Science June 14, 2024 DOI: 10.1021/acsptsci.4c00157 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Citations | 21 |
| Key findings | DOI is a 5-HT2 receptor agonist with historical significance and potential therapeutic applications in neuropsychiatric disorders. |
Abstract
1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI, or DOX where X = -I) was first synthesized in 1973 in a structure-activity study to explore the effect of various aryl substituents on the then newly identified, and subsequently controlled, hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM, or DOX where X = -CH3). Over time, DOI was found to be a serotonin (5-HT) receptor agonist using various peripheral 5-HT receptor tissue assays and later, following the identification of multiple families of central 5-HT receptors, an agonist at 5-HT2 serotonin receptors in rat and, then, human brain. Today, classical hallucinogens, currently referred to as serotonergic psychedelic agents, are receiving considerable attention for their potential therapeutic application in various neuropsychiatric disorders including treatment-resistant depression. Here, we review, for the first time, the historical and current developments that led to DOI becoming a unique, perhaps a landmark, agent in 5-HT2 receptor research.
Comparable studies
Other narrative reviews on serotonin, most cited first.
Citations in the library
Cited by 20
- Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Neuroscience & Biobehavioral Reviews September 20, 2024
- Novel 3-Pyrrolidineindole Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis and Mental Illnesses Such as Depression and Post-Traumatic Stress Disorder. ACS Medicinal Chemistry Letters January 9, 2025
- The utility of 2,5-dimethoxy-4-iodoamphetamine for the study of serotonin 2A and 2C receptors. Molecular Pharmacology 2026
- Novel Indoline Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis, Mental Illness and CNS Disorders. ACS Medicinal Chemistry Letters January 23, 2025
- The Epidemiology of Recreational Use and Availability of DOC and DOI in the United States Journal of Psychoactive Drugs October 9, 2025
and 15 more in the library
Cites 99
- 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Journal of Neuroscience April 15, 1997
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Structure-based discovery of nonhallucinogenic psychedelic analogs Science January 27, 2022
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
and 94 more in the library