Identification of a 5-HT₁ recognition site in human brain membranes different from 5-HT_1A, 5-HT_1B and 5-HT_1C sites

In human caudate and cortex membranes, [³H]serotonin ([³H]5-HT) labels 5-HT_1A and 5-HT_1C recognition sites which show nanomolar affinity for 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) and mesulergine respectively, whereas no 5-HT_1B binding could be identified. However, the majority of the sites labelled by [³H]5-HT (≧ 60% in cortex, 90% in caudate) are different from 5-HT_1A, 5-HT_1B and 5-HT_1C sites. Competition experiments were performed in human caudate membranes incubated with [³H]5-HT in the presence of 100 nM 8-OH-DPAT and 100 nM mesulergine. Under those conditions, [³H]5-HT labelled an apparently homogeneous population of 5-HT₁-like sites which display nanomolar affinity for tryptamines (5-carboxamido-tryptamine, (5-CT) > 5-HT ≧ 5-methoxytryptamine (5-MeOT) > tryptamine) and some ergolines (metergoline > methysergide). In contrast, these sites showed low affinity for drugs with high affinity and/or selectivity for 5-HT_1A (8-OH-DPAT, buspirone), 5-HT_1B (21-009, RU 24969), 5-HT_1C (mesulergine, mianserin) and 5-HT₂ sites (ketanserin, cinanserin). The pharmacological profile of these sites is different from that of 5-HT_1A, 5-HT_1B, 5-HT_1C, 5-HT₂ and 5-HT₃ sites but is consistent with the pharmacology of a 5-HT₁-like receptor. It is very similar to that of the 5-HT_1D site recently described in bovine brain by Heuring and Peroutka.