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

J Pharm Pharmacol. 2004 Feb;56(2):247-55. doi: 10.1211/0022357022575.

Abstract

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.

MeSH terms

  • Animals
  • Cell Line
  • Gene Transfer Techniques
  • Guinea Pigs
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Ileum / drug effects
  • Kidney / cytology
  • Male
  • Membranes / cytology
  • Membranes / drug effects
  • Piperazines / chemical synthesis*
  • Piperazines / pharmacokinetics*
  • Quantitative Structure-Activity Relationship
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / drug effects*
  • Receptor, Serotonin, 5-HT1A / genetics
  • Receptors, Serotonin / drug effects*
  • Serotonin Receptor Agonists / chemical synthesis
  • Serotonin Receptor Agonists / pharmacokinetics

Substances

  • Piperazines
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • serotonin 7 receptor
  • Receptor, Serotonin, 5-HT1A