Substituent branching in phenethylamine-type hallucinogens: a comparison of 1-[2,5-dimethoxy-4-(2-butyl)phenyl]-2-aminopropane and 1-[2,5-dimethoxy-4-(2-methylpropyl)phenyl]-2-aminopropane.
Two novel hallucinogen analogues related to 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM, STP) were synthesized and evaluated in the two-lever drug discrimination paradigm by using 0.08 mg/kg of LSD as the training drug stimulus. The two compounds differ from each other only with respect to the point of branching in the 4-alkyl group. However, pharmacological evaluation revealed a clear difference in difference in potency and degree of LSD generalization for the two isomers. Branching adjacent to the ring, as in the 4-(2-butyl) analogue, may provide steric interference to the formation of the drug-receptor complex, while branching one methylene unit removed from the ring, as in the 4-(2-methylpropyl) analogue, poses less of a steric problem for the drug-receptor interaction. This is consistent with the idea that formation of a charge-transfer complex between the hallucinogen molecule and the receptor may be one of the features of this drug-receptor interaction.
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D000662:Amphetamines / Q000138:chemical synthesis*; D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects; D006213:Hallucinogens / Q000138:chemical synthesis*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000662:Amphetamines; D006213:Hallucinogens; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C041496:1-(2,5-dimethoxy)-4-(2-methylpropyl)phenyl-2-aminopropane; C041495:1-(2,5-dimethoxy-4-(2-butyl)phenyl)-2-aminopropane