Synthesis and evaluation of 2,3-dihydrobenzofuran analogs of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane: drug discrimination studies in rats
David E. Nichols, Andrew J. Hoffman, Robert Oberlender, Robert M. Riggs
Journal of Medicinal Chemistry February 1, 1986 DOI: 10.1021/jm00152a022 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | 6-(2-aminopropyl)-5-methoxy-2 3-dihydrobenzofuran 6-(2-aminopropyl)-5-methoxy-2-methyl-2 |
| Keywords | Citation Icon Altmetrics Social media Library science World wide web |
| Citations | 34 |
| Key points | Two 2,3-dihydrobenzofuran analogues of DOM produced LSD-like stimulus generalization in rats but at doses more than 10-fold higher than DOM. |
Abstract
Two analogues, 6-(2-aminopropyl)-5-methoxy-2,3-dihydrobenzofuran and 6-(2-aminopropyl)-5-methoxy-2-methyl-2,3-dihydrobenzofuran, of the hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) were synthesized and tested in the two-lever drug discrimination paradigm. In rats trained to discriminate saline from LSD tartrate (0.08 mg/kg), stimulus generalization occurred to both of the 2,3-dihydrobenzofuran analogues but at doses more than 10-fold higher than for DOM. A possible explanation for this dramatic attenuation of LSD-like activity could involve a highly directional electrophilic binding site on the receptor that cannot accept the orientation of the unshared electron pairs on the heterocyclic oxygen atom in the benzofurans.