Studies on 1-arylpiperazine derivatives with affinity for rat 5-HT7 and 5-HT1A receptors.
Several 1-aryl-4-(2-arylethyl)piperazine derivatives were synthesized and tested in-vitro for their binding affinity for 5-HT(7) and 5-HT(1A) receptors. These compounds displayed 5-HT(7 )receptor affinity ranging between K(i) = 474 nM and K(i) = 8.2 nM, besides high affinity for the 5-HT(1A) 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) (K(i) = 24.5 and 8.2 nM, respectively) behaved as partial agonist and full agonist, respectively, when tested for 5-HT(7) receptor-mediated relaxation of substance P-induced guinea-pig ileum contraction.
Leopoldo
Marcello
M
Dipartimento Farmaco-Chimico, Università degli Studi di Bari, via Orabona, 4, 70125 Bari, Italy. leopoldo@farmchim.uniba.it
Berardi
Francesco
F
Colabufo
Nicola A
NA
Contino
Marialessandra
M
Lacivita
Enza
E
Perrone
Roberto
R
Tortorella
Vincenzo
V
D000818:Animals; D002460:Cell Line; D018014:Gene Transfer Techniques; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D007668:Kidney / Q000166:cytology; D008297:Male; D008566:Membranes / Q000166:cytology / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D021281:Quantitative Structure-Activity Relationship; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000235:genetics; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis / Q000493:pharmacokinetics
D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A