| 15107597 |
Kovacs A, Gacsalyi I, Wellmann J, Schmidt E, Szucs Z, Dubreuil V, Nicolas JP, Boutin J, Bozsing D, Egyed A, Tihanyi K, Spedding M, Szenasi G: Effects of EGIS-7625, a selective and competitive 5-HT2B receptor antagonist. Cardiovasc Drugs Ther. 2003 Sep-Nov;17(5-6):427-34.
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 rightward 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. |
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