GRANISETRON AND ONDANSETRON - EFFECTS ON THE ILEAL BRAKE MECHANISM INTHE RAT

Studies were carried out on 20 male adult rats to investigate how the action of the selective 5-HT3-receptor antagonists, granisetron and on dansetron, influence gastrointestinal transit under control conditions and when stomach-to-caecum transit was delayed by ileal infusion of l ipid. Stomach-to-caecum transit time (SCTT) was measured using environ mental hydrogen. analysis. Subcutaneous administration of granisetron (BRL 43694, 40, 80 or 150 mug kg-1) significantly delayed the passage of the head of the baked bean meal through the stomach and the small i ntestine under control conditions (P<0.05). Similarly, subcutaneous ad ministration of ondansetron (GR 38032F, 80 or 150 mug kg-1) delayed co ntrol SCTT of the head of the meal but this did not reach statistical significance. In contrast, granisetron significantly reversed the dela y in SCTT induced by ileal infusion of lipid at 40 (P<0.001), 80 (P<0. 01) and 150 mug kg-1 (P<0.05). Ondansetron also reversed the lipid-ind uced delay at 40 (P<0.01), 80 (P<0.00 1) and 150 mug kg-1 (P<0.001). T hese apparently conflicting results may be rationalized by postulating the presence of 5-HT3 receptors on afferent nerves which, when inhibi ted by the specific antagonists, initiate reflexes that both accelerat e and delay transit.