Premium
Stimulation of Canine Gastric Motility by BRL 24924, a New Gastric Prokinetic Agent
Author(s) -
Bermudez J.,
Dunbar A.,
Sanger G. J.,
Turner D. H.
Publication year - 1990
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.1990.tb00036.x
Subject(s) - hexamethonium , metoclopramide , gastric emptying , propranolol , atropine , granisetron , phentolamine , medicine , stimulation , chemistry , endocrinology , pharmacology , domperidone , antiemetic , stomach , dopamine , vomiting
We describe the actions and pharmacology of BRL 24924, a new gastric prokinetic agent, in conscious dogs. In Heidenhain pouch preparations, BRL 24924 (0.01–0.16 mg/kg i.v.) is a potent stimulant of interdigestive phasic motility (increases in intraluminal pressure), approximately 50 times more potent than metoclopramide. The stimulatory effect of BRL 24924 (0.025 mg/kg i.v.) was prevented by atropine (0.1 mg/kg s.c.). It was initially unaffected by hexamethonium (5 mg/kg i.v.), but hexamethonium prevented BRL 24924 from causing sustained stimulation of motility. The stimulatory activity of BRL 24924 (0.025 mg/kg i.v.) was unaffected by propranolol (3 mg/kg i.v.) or by phentolamine (1 mg/kg i.v.). The selective 5‐hydroxytryptamine 3 receptor antagonist granisetron (BRL 43694; 0.1 or 1.0 mg/kg i.v.) neither mimicked nor prevented the stimulatory actions of BRL 24924. In dogs with a gastric fistula, the gastric emptying of a liquid test meal was accelerated following BRL 24924 (0.1 mg/kg i.v.) but was unaffected by granisetron (0.1 and 1 mg/kg i.v.). We conclude that BRL 24924 is a potent, long‐lasting, and effective stimulant of canine gastric motility, which accelerates gastric emptying. The pharmacology of BRL 24924 is discussed in terms of its relationship with myenteric 5‐hydroxytryptamine receptors.