Cardiovascular Drugs and Therapy

, Volume 17, Issue 5, pp 427–434

Effects of EGIS-7625, a Selective and Competitive 5-HT2B Receptor Antagonist

  • Anikó Kovács
  • Istvan Gacsályi
  • János Wellmann
  • Éva Schmidt
  • Zsuzsanna Szücs
  • Valérie Dubreuil
  • Jean Paul Nicolas
  • Jean Boutin
  • Daniel Bózsing
  • Andras Egyed
  • Kasoly Tihanyi
  • Michael Spedding
  • Gábor Szénási
Article

DOI: 10.1023/B:CARD.0000015857.96371.43

Cite this article as:
Kovács, A., Gacsályi, I., Wellmann, J. et al. Cardiovasc Drugs Ther (2003) 17: 427. doi:10.1023/B:CARD.0000015857.96371.43

Abstract

Our aim was to specify the 5-HT2 subtype selectivity of EGIS-7625 (1-benzyl-4-[(2-nitro-4-methyl-5-amino)-phenyl]-piperazine), a new 5-HT2B ligand, in receptor binding studies and characterize its pharmacology at 5-HT2A, 5-HT2B and 5-HT2C receptors in in vivo experiments and in isolated organs, in vitro. EGIS-7625 had high affinity for recombinant human 5-HT2B receptors (pKi = 9.0) but much weaker affinity for 5-HT2A and 5-HT2C receptors (pKi = 6.2 and 7.7, respectively). In the classic 5-HT2B test, EGIS-7625 produced a concentration-related parallel rightward shift in the concentration-response relationship for the 5-HT-induced smooth muscle constriction in rat stomach fundus strips with a pA2 of 9.4. On the other hand, EGIS-7625 was a weak competitive antagonist at 5-HT2A receptors as it shifted 5-HT-induced concentration-response curves to the right at high concentrations (pA2 = 6.7) in rabbit pulmonary artery strips. The m-chlorophenylpiperazine-induced hypomotility and hypophagia was only partially attenuated by EGIS-7625 even at a dose of 30 mg/kg i.p. while mianserin, a non-selective 5-HT antagonist was almost fully effective in these tests at 3 mg/kg i.p., suggesting weak antagonistic effect of EGIS-7625 at neuronal 5-HT2C receptors, in vivo. In conclusion, EGIS-7625 is a potent, selective and competitive 5-HT2B antagonist that seems to be a good research tool for the separation of the functional roles of vascular 5-HT2A and 5-HT2B receptors.

serotoninrat stomach fundusrabbit pulmonary arteryrecombinant human 5-HT2 receptors

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Anikó Kovács
    • 1
  • Istvan Gacsályi
    • 1
  • János Wellmann
    • 1
  • Éva Schmidt
    • 1
  • Zsuzsanna Szücs
    • 1
  • Valérie Dubreuil
    • 2
  • Jean Paul Nicolas
    • 2
  • Jean Boutin
    • 2
  • Daniel Bózsing
    • 1
  • Andras Egyed
    • 1
  • Kasoly Tihanyi
    • 1
  • Michael Spedding
    • 2
  • Gábor Szénási
    • 1
  1. 1.Division of Preclinical Research, EGIS Pharmaceuticals LtdFrance
  2. 2.Institut de Recherches Internationales Servier, Croissy sur SeineFrance