Studies on 1-arylpiperazine derivatives with affinity for rat 5-HT7 and 5-HT1A receptors


Dipartimento Farmaco-Chimico, Università degli Studi di Bari, via Orabona, 4, 70125 Bari, Italy. E-mail:


Several 1-aryl-4-(2-arylethyl)piperazine derivatives were synthesized and tested in-vitro for their binding affinity for 5-HT7 and 5-HT1A receptors. These compounds displayed 5-HT7 receptor affinity ranging between Ki = 474 nm and Ki = 8.2 nm, besides high affinity for the 5-HT1A receptor. Intrinsic activity of the most potent compounds was assessed. 4-[2-(3-Methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (16) and 1-(1,2-benzisoxazol-3-yl)-4-[2-(3-methoxyphenyl)ethyl]piperazine (20) (Ki = 24.5 and 8.2 nm, respectively) behaved as partial agonist and full agonist, respectively, when tested for 5-HT7 receptor-mediated relaxation of substance P-induced guinea-pig ileum contraction.