Structure-activity relationship studies of CNS agents-XVII. Spiro[piperidine-4′,1-(1,2,3,4-tetrahydro-β-carboline)] as a probe defining the extended topographic model of 5-HT1A receptors Original Research Article

Spiro[piperidine-4′,1-(1,2,3,4-tetrahydro-β-carboline)] (10), its derivatives 11–15 and its analogs 16 and 17 were examined as ligands of serotonin 5-HT1A receptors. It was shown that compounds 12 and 14 had essentially the same 5-HT1A affinity as 1-phenylpiperazine and its rigid analog 7, whereas there were substantial differences in the steric arrangement of their crucial pharmacophores, i.e. aromatic and protonation centers. On the basis of the existing models and using the (+)-LSD structure as a template, a new, extended three-point topographic model of 5-HT1A receptors has been proposed.