Serotonin receptor affinities of psychoactive phenalkylamine analogues.
Employing a rat fundus model, the serotonin (5-HT) receptor affinities of 45 phenalkylamine analogues were determined. Phenethylamine and phenylisopropylamine possess relatively low receptor affinities; in general, mono-, di-, and trimethoxylation enhance affinity. Of the disubstituted compounds, methoxyl groups at the 2 and 5 positions are optimal for imparting a high affinity. 4-Methylation, 4-ethylation and 4-bromination also enhance receptor affinity, while N,N-dimethylation of the terminal amine decreases affinity. alpha-Methylation of phenethylamines has little effect on affinity when racemates are examined. Introduction of a benzylic keto group can either increase or decrease affinity, depending upon the presence of other aromatic substituents. The most behaviorally active compounds were found to possess the highest 5-HT receptor affinities, while less active compounds were found to possess lower affinities.
D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006213:Hallucinogens / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects; D013329:Structure-Activity Relationship
D000588:Amines; D006213:Hallucinogens; D011985:Receptors, Serotonin