5-HT1 and 5-HT2 Binding Characteristics of 1-(2,5-Dimethoxy-4-bromophenyl)-2-aminopropane Analogues

Article abstract of DOI:10.1021/jm00152a005

1-(2,5-Dimethoxy-4-bromophenyl)-2-aminopropane (DOB; 1a) is a purported serotonin (5-HT) agonist that binds selectively to central 5-HT₂ binding sites.Systematic removal of any or all of the aromatic substituents had relatively little effect on 5-HT₁ binding but reduced 5-HT₂ binding by approximately 2 or more orders of magnitude.Demethylation of the 2-methoxy group of 1a, or introduction of N-n-propyl group, doubled 5-HT₁-site affinity but decreased 5-HT₂-site affinity by 3- and 30-fold, respectively.In tests of stimulus generalization, using rats trained to discriminate DOM from saline, the 2-demethyl and N-propyl derivatives were found to produce stimulus effects similar to those of DOB.In addition, the S-(+) isomer of the iodo analogue of 1a was found to possess one-third the affinity of its R-(-) enantiomer at 5-HT₂ sites and also resulted in DOM-stimulus generalization.Of the DOB analogues examined, DOB (1a) possesses optimal selectivity for 5-HT₂ binding.