ISSN:
1432-1912
Keywords:
Key words 5-HT4 receptors
;
Gastric emptying
;
Benzamides
;
SC 49518
;
SC 53116
;
RS 23597-190
;
SB 204070
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract It is well documented that certain substituted benzamides, such as cisapride, and benzimidazolones, such as BIMU 8, enhance gastric emptying in rats. As these compounds possess 5-HT3 antagonistic and 5-HT4 agonistic properties, the precise mechanisms (5-HT3 or 5-HT4) underlying their gastroprokinetic effects is still unclear. In the present study, we used SC 49518 (a benzamide and selective 5-HT4 receptor agonist) and two selective 5-HT4 receptor antagonists (RS 23597-190 and SB 204070) to elucidate the role of 5-HT4 receptors in gastroprokinesis. SC 49518 (1–316 μg/kg; ip) produced significant and dose-dependent stimulation of gastric emptying in rats (ED50=2.3 μg/kg; ip). SC 49518 also produced dose-dependent inhibition of bradycardia induced by 2-methyl 5-HT (von Bezold-Jarisch reflex) but with a 156 fold lower potency (ID50=0.36 mg/kg; ip). The gastroprokinetic effects of SC 49518 (3–316 μg/kg; ip) were significantly antagonized by the selective 5-HT4 receptor antagonist RS 23597-190 (0.1 mg/kg/min; iv). SB 204070 (0.003–1 mg/kg; ip), another selective 5-HT4 receptor antagonist, produced dose-dependent inhibition of the gastroprokinetic effects of SC 49518 (10 μg/kg; ip), the inhibition attaining statistical significance at the dose of 0.1 mg/kg; ip. RS 23597-190 had no effects on gastric emptying per se whereas SB 204070 significantly increased gastric emptying by itself at 1 mg/kg; ip but not at 0.1 mg/kg; ip. These findings show, for the first time, that SC 49518, a selective 5-HT4 receptor agonist, produces potent stimulation of gastric emptying in rats via a mechanism involving activation of 5-HT4 receptors. It is suggested that a similar mechanism may account for the gastro-prokinetic effects of other non-selective benzamides and benzimidazolones.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00170157
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