| Autor: |
Kovács, Anikó, Gacsályi, Istvan, Wellmann, János, Schmidt, Éva, Szücs, Zsuzsanna, Dubreuil, Valérie, Nicolas, Jean, Boutin, Jean, Bózsing, Daniel, Egyed, Andras, Tihanyi, Kasoly, Spedding, Michael, Szénási, Gábor |
| Zdroj: |
Cardiovascular Drugs and Therapy; September 2003, Vol. 17 Issue: 5-6 p427-434, 8p |
| Abstrakt: |
Our aim was to specify the 5-HT2subtype selectivity of EGIS-7625 (1-benzyl-4-[(2-nitro-4-methyl-5-amino)-phenyl]-piperazine), a new 5-HT2Bligand, in receptor binding studies and characterize its pharmacology at 5-HT2A, 5-HT2Band 5-HT2Creceptors in in vivoexperiments and in isolated organs, in vitro. EGIS-7625 had high affinity for recombinant human 5-HT2Breceptors (pKi= 9.0) but much weaker affinity for 5-HT2Aand 5-HT2Creceptors (pKi= 6.2 and 7.7, respectively). In the classic 5-HT2Btest, 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 pA2of 9.4. On the other hand, EGIS-7625 was a weak competitive antagonist at 5-HT2Areceptors 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-HT2Creceptors, in vivo. In conclusion, EGIS-7625 is a potent, selective and competitive 5-HT2Bantagonist that seems to be a good research tool for the separation of the functional roles of vascular 5-HT2Aand 5-HT2Breceptors. |
| Databáze: |
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