title: VB20B7, a novel 5-HT-ergic agent with gastrokinetic activity. II. Evaluation of the gastroprokinetic activity in rats and dogs.
abstract: The gastrokinetic activity of 2[1-(4-piperonyl)piperazinyl]benzothiazole (VB20B7), a new compound with 5-HT4 receptor agonist and weak 5-HT3 receptor antagonist properties has been studied in rats and dogs. The effects of VB20B7 were investigated in physiological conditions and in a model of gastroparesis induced by the alpha 2-adrenergic agonist UK-14304 and compared with cisapride. In rats, both VB20B7 and cisapride enhanced gastric emptying of indigestible solids (steel spheroids) and liquids (phenol red) at doses of 5-10 mg kg-1 by mouth. Gastric emptying of solid radiopaque markers in fasted beagle dogs was enhanced significantly by VB20B7 (0.25-1 mg kg-1 p.o.) whereas the effect of cisapride (0.5-2 mg kg-1 p.o.) did not reach statistical significance. Similar results were found when the radiopaque markers were given to the dogs following a standard solid meal. The delayed gastric emptying of indigestible solids and radiopaque markers by UK-14304 was reversed by oral administration of VB20B7 in both rats and dogs. Cisapride, however, was only effective in rats. In addition, gastric emptying of a digestible solid/liquid meal was assessed by quantitating the rate of appearance of the radioactive markers in the duodenum of dogs. VB20B7 (0.2-1 mg kg-1, i.v.) enhanced gastric emptying of both solid and liquid phases while cisapride only enhanced emptying of the solid phase. The present study indicates that acute oral and intravenous administration of VB20B7 accelerates gastric emptying of both solids and liquids in different animal models.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: García-Garayoa
authors.forename: A
authors.initials: A
authors.lastname: Monge
authors.forename: J
authors.initials: J
authors.lastname: Roca
authors.forename: J
authors.initials: J
authors.lastname: Del Río
authors.forename: B
authors.initials: B
authors.lastname: Lasheras
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D052160:Benzothiazoles; D001831:Body Temperature / Q000187:drug effects; D000068438:Brimonidine Tartrate; D004285:Dogs; D005260:Female; D005289:Ferrets; D005746:Gastric Emptying / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D000932:Antiemetics; D052160:Benzothiazoles; D005765:Gastrointestinal Agents; D010879:Piperazines; D011810:Quinoxalines; D011985:Receptors, Serotonin; D013844:Thiazoles; C087141:2-(1-(4-piperonyl)piperazinyl)benzothiazole; D000068438:Brimonidine Tartrate