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, G. Szénási

Research output: Contribution to journalArticle

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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 - 2003

Fingerprint

Receptor, Serotonin, 5-HT2B
Serotonin
Receptor, Serotonin, 5-HT2C
Serotonin Antagonists
Mianserin
EGIS7625
Receptor, Serotonin, 5-HT2A
Constriction
Pulmonary Artery
Smooth Muscle
Blood Vessels
Stomach

Keywords

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

ASJC Scopus subject areas

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

Cite this

Effects of EGIS-7625, a selective and competitive 5-HT 2B receptor antagonist. / Kovács, Anikó; Gacsályi, Istvan; Wellmann, János; Schmidt, Éva; Szücs, Zsuzsanna; Dubreuil, Valérie; Nicolas, Jean Paul; Boutin, Jean; Bózsing, Daniel; Egyed, Andras; Tihanyi, Kasoly; Spedding, Michael; Szénási, G.

In: Cardiovascular Drugs and Therapy, Vol. 17, No. 5-6, 2003, p. 427-434.

Research output: Contribution to journalArticle

Kovács, A, Gacsályi, I, Wellmann, J, Schmidt, É, Szücs, Z, Dubreuil, V, Nicolas, JP, 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, vol. 17, no. 5-6, pp. 427-434. https://doi.org/10.1023/B:CARD.0000015857.96371.43
Kovács, Anikó ; Gacsályi, Istvan ; Wellmann, János ; Schmidt, Éva ; Szücs, Zsuzsanna ; Dubreuil, Valérie ; Nicolas, Jean Paul ; Boutin, Jean ; Bózsing, Daniel ; Egyed, Andras ; Tihanyi, Kasoly ; Spedding, Michael ; Szénási, G. / Effects of EGIS-7625, a selective and competitive 5-HT 2B receptor antagonist. In: Cardiovascular Drugs and Therapy. 2003 ; Vol. 17, No. 5-6. pp. 427-434.
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AU - Szücs, Zsuzsanna

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AU - Nicolas, Jean Paul

AU - Boutin, Jean

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