| Autor: |
Csillik-Perczel, Viola, Bakonyi, Anna, Yemane, Tilahun, Vitalis, Beata, Horvath, Edith, Solyom, Sandor, Szekely, Jozsef I., Harsing Jr, Laszlo G. |
| Zdroj: |
Pharmacology & Toxicology; 1996, Vol. 79 Issue 1, p32-39, 8p |
| Abstrakt: |
The effects of GYKI-46 903 ((+)endo-4-propionyloxy-6-(4-fluorophenyl)-1-azabicyclo [3.3.1]non-6-ene HCI), on 5-HT3 receptors have been studied and compared with ondansetron in peripheral organs in vitro and in vivo, and in a receptor binding assay in membranes prepared from rat cerebral cortex. GYKI-46 903 was found to be a non-competitive antagonist at 5-HT3 receptors present in non-stimulated longitudinal muscle strip of guinea-pig ileum (pD2'against serotonin=5.54), and also in 5-methoxytryptamine-pretreated electrically stimulated ileal preparations (pD2'against serotonin=5.26). On the contrary, ondansetron was found to be a competitive antagonist for 5-HT3 receptors; the pA2 value against serotonin was 7.40 in non-stimulated ileum, and it was 7.08 in electrically stimulated ileal preparation pretreated with 5-methoxytryptamine. In displacement studies, the pIC50 values of GYKI-46 903 and ondansetron against [3H]granisetron binding to rat cerebral cortex membranes were 6.91 and 8.58 respectively. GYKI-46 903, when administered by intravenous infusion, antagonized the decrease in heart rate evoked by serotonin (Bezold-Jarisch reflex) in anaesthetized rats, and the maximal reversal was less than 50%. This was in striking contrast with ondansetron, which, after intravenous injection, completely antagonized the serotonin-induced bradycardia with an ID50 value of 3.28 ug/kg. These data classify GYKI-46 903 as a non-competitive antagonist for 5-HT3 receptors. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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