Effects of EGIS-7625, a selective and competitive 5-HT 2B 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

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5 Citations (Scopus)

Abstract

Our aim was to specify the 5-HT 2 subtype selectivity of EGIS-7625 (1-benzyl-4-[(2-nitro-4-methyl-5-amino)-phenyl]-piperazine), a new 5-HT 2B ligand, in receptor binding studies and characterize its pharmacology at 5-HT 2A, 5-HT 2B and 5-HT 2C receptors in in vivo experiments and in isolated organs, in vitro. EGIS-7625 had high affinity for recombinant human 5-HT 2B receptors (pK i = 9.0) but much weaker affinity for 5-HT 2A and 5-HT 2C receptors (pK i = 6.2 and 7.7, respectively). In the classic 5-HT 2B test, EGIS-7625 produced a concentration-related parallel right-ward shift in the concentration-response relationship for the 5-HT-induced smooth muscle constriction in rat stomach fundus strips with a pA 2 of 9.4. On the other hand, EGIS-7625 was a weak competitive antagonist at 5-HT 2A receptors as it shifted 5-HT-induced concentration-response curves to the right at high concentrations (pA 2 = 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-HT 2C receptors, in vivo. In conclusion, EGIS-7625 is a potent, selective and competitive 5-HT 2B antagonist that seems to be a good research tool for the separation of the functional roles of vascular 5-HT 2A and 5-HT 2B receptors.

Original languageEnglish
Pages (from-to)427-434
Number of pages8
JournalCardiovascular Drugs and Therapy
Volume17
Issue number5-6
DOIs
Publication statusPublished - Dec 1 2003

Keywords

  • Rabbit pulmonary artery
  • Rat stomach fundus
  • Recombinant human 5-HT receptors
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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    Kovács, A., Gacsályi, I., Wellmann, J., Schmidt, É., Szücs, Z., Dubreuil, V., Nicolas, J. P., Boutin, J., Bózsing, D., Egyed, A., Tihanyi, K., Spedding, M., & Szénási, G. (2003). Effects of EGIS-7625, a selective and competitive 5-HT 2B receptor antagonist. Cardiovascular Drugs and Therapy, 17(5-6), 427-434. https://doi.org/10.1023/B:CARD.0000015857.96371.43