ACS pharmacology & translational science
June 14, 2024
Richard A Glennon, Małgorzata Dukat
21 citations
The compound DOI, first synthesized in 1973, is a serotonin receptor agonist, specifically acting at 5-HT2 receptors in rat and human brain. It emerged from research on hallucinogenic agents and is now studied for potential therapeutic use in neuropsychiatric disorders such as treatment-resistant depression. This review traces the historical and current developments that made DOI a landmark agent in 5-HT2 receptor research.
Pharmacology, biochemistry, and behavior
August 1, 2004
Nantaka Khorana, Manik R Pullagurla, Malgorzata Dukat et al.
21 citations
Two sulfur-containing phenylalkylamines, 4-MTA and 2C-T-7, gaining popularity on the illicit drug market, were tested in rats trained to discriminate the hallucinogen DOM, the stimulant cocaine, or the empathogen MDMA from a neutral substance. 4-MTA and its analog 4-MTMA substituted only for MDMA, whereas 2C-T-7 substituted only for DOM. These results indicate that 4-MTA and 4-MTMA act like MDMA, while 2C-T-7 behaves like a DOM-like hallucinogen, extending knowledge of structure-activity relationships and aligning with limited human reports.
Frontiers in pharmacology
January 1, 2023
Prithvi Hemanth, Pallavi Nistala, Vy T Nguyen et al.
4 citations
For a series of 13 compounds related to the psychedelic agent 2,5-DMA, rat brain 5-HT2 receptor affinities correlate strongly with human 5-HT2A (r = 0.942) and 5-HT2B (r = 0.916) affinities. Human 5-HT2A affinity also correlates with the lipophilicity of the 4-position substituent (r = 0.798). In functional assays, eight of ten compounds acted as agonists at the human 5-HT2B receptor, while two acted as antagonists. Human 5-HT2B affinity, but not agonist action, correlates with substituent lipophilicity (r = 0.750). Rat and human 5-HT2A affinity may approximate human 5-HT2B affinity but cannot predict agonist action. Some 2,5-DMA analogs on the clandestine market may pose cardiac valvulopathy risk with chronic use via h5-HT2B activation.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
February 2, 2026
Maya C Gaines-Smith, Justin M Silverman, Michael Fiorillo et al.
3 citations
The drug MDMA, also known as ecstasy, is being studied as a possible aid in psychotherapy for hard-to-treat mental health conditions, but how it works in the brain is not fully understood. In experiments with mice, the S(+) form of MDMA, but not the R(-) form, activated a specific serotonin receptor (5-HT2AR) and caused changes in brain cell connections in the frontal cortex of males. The R(-) form had little effect except for a head-twitch response in females. Blocking the serotonin transporter with fluoxetine prevented these effects, showing that MDMA works indirectly by increasing serotonin levels. These results reveal that MDMA's effects on brain plasticity depend on both the drug's chemical form and the sex of the animal.
ACS pharmacology & translational science
December 8, 2023
Richard A Glennon, Mal Gorzata Dukat
3 citations
Alpha-ethyltryptamine (AET), a centrally acting agent known for over 75 years, was briefly marketed as an antidepressant before being withdrawn and classified as a U.S. Schedule I substance due to concerns about abuse and toxicity. Amid current interest in hallucinogenic tryptamines for treating neuropsychiatric disorders like treatment-resistant depression and anxiety, this review critically examines AET's history and argues that it may have been ahead of its time. AET possesses many antidepressant hallmarks, suggesting that its derivatives and optical isomers warrant further investigation.
Psychopharmacology
June 1, 2025
Carmen Abate, Richard Young, Malgorzata Dukat et al.
2 citations
The drug α-ethyltryptamine (α-ET), once used as an antidepressant and structurally related to the hallucinogen α-methyltryptamine, produces stimulus effects in rats that are similar to those of the phenylalkylamines MDMA (Ecstasy) and MDA (Love Drug). Rats trained to discriminate α-ET from saline showed full generalization to both MDMA and MDA. Four synthetic analogs of α-ET produced varied results: 4-OMe α-ET showed negligible α-ET-like effects, 5-OMe α-ET modest effects, while 6-OMe α-ET and 7-OMe α-ET fully generalized but with a narrow dose range for the former. α-ET appears to exert a complex stimulus combining features of MDMA, MDA, hallucinogens, and stimulants, suggesting it is a tryptamine counterpart to these phenylalkylamines.