Behavioral and serotonin receptor properties of 4-substituted derivatives of the hallucinogen 1-(2,5-dimethoxyphenyl)-2-aminopropane.
Richard A Glennon, R Young, F Benington, R D Morin
Journal of Medicinal Chemistry October 1982 DOI: 10.1021/jm00352a013 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical pharmacology study (receptor binding and drug discrimination in rats) Qualitative Peer reviewed |
|---|---|
| Population | Rats trained to discriminate DOM from saline; 5-HT receptor preparations |
| Interventions | 4-substituted 2 OMe OEt Me Et F Br I DOM |
| Measures | 5-HT receptor affinity, ED50 from drug discrimination |
| Topics | Serotonin |
| Key points | Substituent lipophilicity at the 4-position of 2,5-DMA had minimal effect on 5-HT receptor affinity or behavioral activity. Derivatives most potent in humans showed significant 5-HT receptor affinity, and rats trained to discriminate DOM generalized to the 4-substituted 2,5-DMA derivatives. The authors argue that the DOM discrimination paradigm, whose ED50 values track human hallucinogenic potency, is a useful tool for comparing hallucinogenic agents. |
Abstract
The serotonin (5-HT) receptor affinities and behavioral (discriminative stimulus) properties of a series of 4-substituted derivatives of 1-(2,5-dimethoxyphenyl)-2-aminopropanes (2,5-DMA) were investigated. The substituents at the 4-position included H, OMe, OEt, Me, Et, F, Br, I, and NO2. Substituent lipophilicities (pi values) of these functionalities appear to have a minimal effect on either 5-HT receptor affinity or behavioral activity. Those derivatives previously found to be most potent in human studies possess significant affinity for 5-HT receptors. Furthermore, when rats trained to discriminate (+/-)-1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline were used, generalization was found to occur upon administration of the 4-substituted 2,5-DMA derivatives. Because a direct relationship exists between the ED50 values obtained from these discrimination studies and human hallucinogenic potencies, the discriminative stimulus paradigm, with DOM as a training drug, appears to be a useful tool for comparing the quantitative and qualitative (DOM-like) effects produced by certain hallucinogenic agents.
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| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 34
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology May 1, 2020
- Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups Journal of Medicinal Chemistry 1996
- Dihydrobenzofuran Analogues of Hallucinogens. 4. Mescaline Derivatives Journal of Medicinal Chemistry September 1, 1997
- [125I]-2-(2,5-dimethoxy-4-iodophenyl)aminoethane ([125I]-2C-I) as a label for the 5-HT2 receptor in rat frontal cortex. Pharmacology, Biochemistry, and Behavior 1990
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