GYKI-46903, a non-competitive antagonist for 5-HT3 receptors

Viola Csillik-Perczel, Anna Bakonyi, Tilahun Yemane, Beata Vitalis, Edith Horvath, Sandor Solyom, Jozsef I. Szekely, L. Hársing

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The effects of GYKI-46903 ((+)endo-4-propionyloxy-6-(4-fluorophenyl)-1-azabicyclo [3.3.1]non-6-ene HCl), 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-46903 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-46903 and ondansetron against [3H]granisetron binding to rat cerebral cortex membranes were 6.91 and 8.58 respectively. GYKI-46903, 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-46903 as a non-competitive antagonist for 5-HT3 receptors.

Original languageEnglish
Pages (from-to)32-39
Number of pages8
JournalPharmacology and Toxicology
Volume79
Issue number1
Publication statusPublished - 1996

Fingerprint

Receptors, Serotonin, 5-HT3
Ondansetron
Serotonin
5-Methoxytryptamine
Rats
Ileum
Cerebral Cortex
Granisetron
Membranes
Bradycardia
Intravenous Infusions
Intravenous Injections
Reflex
Muscle
Assays
Guinea Pigs
Heart Rate
GYKI 46903
Muscles

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Pharmacology
  • Toxicology

Cite this

Csillik-Perczel, V., Bakonyi, A., Yemane, T., Vitalis, B., Horvath, E., Solyom, S., ... Hársing, L. (1996). GYKI-46903, a non-competitive antagonist for 5-HT3 receptors. Pharmacology and Toxicology, 79(1), 32-39.

GYKI-46903, a non-competitive antagonist for 5-HT3 receptors. / Csillik-Perczel, Viola; Bakonyi, Anna; Yemane, Tilahun; Vitalis, Beata; Horvath, Edith; Solyom, Sandor; Szekely, Jozsef I.; Hársing, L.

In: Pharmacology and Toxicology, Vol. 79, No. 1, 1996, p. 32-39.

Research output: Contribution to journalArticle

Csillik-Perczel, V, Bakonyi, A, Yemane, T, Vitalis, B, Horvath, E, Solyom, S, Szekely, JI & Hársing, L 1996, 'GYKI-46903, a non-competitive antagonist for 5-HT3 receptors', Pharmacology and Toxicology, vol. 79, no. 1, pp. 32-39.
Csillik-Perczel V, Bakonyi A, Yemane T, Vitalis B, Horvath E, Solyom S et al. GYKI-46903, a non-competitive antagonist for 5-HT3 receptors. Pharmacology and Toxicology. 1996;79(1):32-39.
Csillik-Perczel, Viola ; Bakonyi, Anna ; Yemane, Tilahun ; Vitalis, Beata ; Horvath, Edith ; Solyom, Sandor ; Szekely, Jozsef I. ; Hársing, L. / GYKI-46903, a non-competitive antagonist for 5-HT3 receptors. In: Pharmacology and Toxicology. 1996 ; Vol. 79, No. 1. pp. 32-39.
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