INFLUENCE OF AMINE SUBSTITUENTS ON 5-HT2A VERSUS 5-HT2C BINDING OF PHENYLALKYLAMINES AND INDOLYLALKYLAMINES

The effect of 15 different amine substituents on 5-HT2A and 5-HT2C ser otonin receptor binding was investigated for two series of compounds ( i.e., phenylalkylamine and indolylalkylamine derivatives). In general, amine substitution decreases receptor affinity; however, N-(4-bromobe nzyl) substitution results in compounds that bind at 5-HT2A receptors with high affinity (K-i < 1 nM) and with >100-fold selectivity. Althou gh parallel structural modifications in the two series result in paral lel shifts in 5-HT2C binding, these same modifications alter 5-HT2A bi nding in a less consistent manner.