Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes

摘要: Affinities of drugs for 21 indolealkylamine derivatives, some with putative hallucinogenic activity, were determined at 5-HT1A, 5-HT2A and 5-HT2B recognition sites, using radioligand competition studies. Nearly all the derivatives displayed greatest potency receptor, labelled by [125I]R-(−)DOI in cortex rat. Most 2–10 times lower affinity HT2B receptor [3H]ketanserin bovine cortex. Derivatives lacking ring substituents affinities compared to substituted 4- or 5-position indole ring. The 4-hydroxylated 25-380-fold selectivity site, vs 5-HT1A while 5-substituted approximately equal sites. Affinity compounds site was greater than 300 nM. 6-substituted micromolar 5-HT sites examined. size N,N-dialkyl substituent a secondary determinant affinity, groups larger N,N-diisopropyl resulting marked reduction both This study demonstrated that 4-hydroxy-indolealkylamines, like psychotomimetic phenylisopropylamines, bind potently selectively [125I]R-(−)DOI. provides further evidence indicating this recently described subtype 5-HT2 may partially mediate action agents.