Synthesis and evaluation of 2,3-dihydrobenzofuran analogues of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane: drug discrimination studies in rats.
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.
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D006213:Hallucinogens / Q000138:chemical synthesis / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000662:Amphetamines; D001572:Benzofurans; D006213:Hallucinogens; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D008238:Lysergic Acid Diethylamide