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.
ACS pharmacology & translational science – June 14, 2024
Source: PubMed
Summary
DOI, a compound first synthesized in 1973, has emerged as a significant serotonin receptor agonist, particularly at the 5-HT2 receptors, impacting both rat and human brains. Its unique properties have sparked interest in its potential therapeutic applications for neuropsychiatric disorders, including treatment-resistant depression. With an increasing focus on serotonergic psychedelics, DOI stands out as a landmark agent in this field. Historical and contemporary developments highlight its role in advancing understanding of serotonin receptors, with implications for innovative mental health treatments.
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.