STRUTURE-ACTIVITY RELATIONSHIP STUDIES OF CNS AGENTS .26. CARBOXAMIDO)ETHYL]-1-(2-METHOXYPHENYL)-PIPERAZINES - HIGH-AFFINITY 5-HT1A AGONISTS

ecarboxamido)ethyl]-1-(2-methoxyphenyl)piperazines 8a-c, 8e, and 8h we re obtained by acylation of 4-(2-aminoethyl)-1-(2-methoxyphenyl)pipera zine, and their 5-HT1A, 5-HT2A and alpha(1) receptor affinities were d etermined. It was found that the terminal cycloalkane moiety strongly stabilizes both the 5-HT1A and 5-HT2A receptor-ligand complexes. It wa s demonstrated that the most active 5-HT1A ligands 8e and 8h (K-i = 2. 1 and 0.21 nM, respectively) behaved as potent agonists of these recep tors, i.e. both derivatives mimicked 8-OH-DPAT in the lower lip retrac tion (LLR) model and the effect was susceptible to blockade by reasona ble doses of the selective 5-HT1A receptor antagonist (S)-WAY-100135.