NEW BENZOCYCLOALKYLPIPERAZINES, POTENT AND SELECTIVE 5-HT1A ACCEPTOR LIGANDS

A series of 1-(benzocycloalkyl)-4-(benzamidoalkyl)piperazine derivativ es was prepared in order to obtain compounds with a high affinity and selectivity for 5-HT1A receptors. The modifications of aromatic substi tuents, the length of the alkyl chain, and the size of the ring were e xplored. Most of tetrahydronaphthyl)-N'-(benzamidoethyl)piperazines (3 2-37) were bound to 5-HT1A receptors in a nanomolar range and presente d a high degree of selectivity. After resolution, levorotatory enantio mers showed affinity and selectivity higher than those of dextrorotato ry ones for 5-HT1A sites. The agonist type activity of selected deriva tives was also confirmed in vitro on the inhibition of the activation of adenylate cyclase induced by forskolin and, in vivo, on the inducti on of the lower lip retraction in rats.