The effects of granisetron, ICS 205-930 and ondansetron on the visceral pain reflex induced by duodenal distension.
1. Distension of the duodenum in anaesthetized rats, by rapid application of intraluminal pressures (10-75 cmH2O), evoked falls in diastolic blood pressure and intragastric pressure. 2. The distension-induced responses were blocked by pretreatment with morphine (20 mg kg-1, s.c.), an action reversible by injection of naloxone (5 mg kg-1, i.v.). 3. Bilateral cervical vagotomy reduced the distension-evoked fall in intragastric pressure but had no effect on the corresponding fall in blood pressure. 4. Granisetron or ICS 205-930 (1-1000 micrograms kg-1, i.v.) had no effects on duodenal intraluminal pressure, but reduced the responses to distension with a bell-shaped dose-response relationship. Ondansetron (1-1000 micrograms kg-1, i.v.) did not reduce the reflex responses. 5. These results show that the 5-HT3 receptor antagonists used exerted different effects on the reflex responses to duodenal distension.
Moss
H E
HE
Beecham Pharmaceuticals, Medicinal Research Centre, Harlow, Essex.
Sanger
G J
GJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004386:Duodenum / Q000187:drug effects; D017829:Granisetron; D007093:Imidazoles / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D017294:Ondansetron; D010146:Pain / Q000503:physiopathology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects; D000077526:Tropisetron; D014628:Vagotomy
D017829:Granisetron; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D009020:Morphine; D017294:Ondansetron; D011720:Pyrazoles; D012702:Serotonin Antagonists; D000077526:Tropisetron