VB20B7, A NOVEL 5-HT-ERGIC AGENT WITH GASTROKINETIC ACTIVITY .2. EVALUATION OF THE GASTROPROKINETIC ACTIVITY IN RATS AND DOGS

The gastrokinetic activity of 2[1-(4-piperonyl)piperazinyl]benzothiazo (VB20B7), a new compound with 5-HT4 receptor agonist and weak 5-HT3 r eceptor antagonist properties has been studied in rats and dogs. The e ffects of VB20B7 were investigated in physiological conditions and in a model of gastroparesis induced by the alpha(2)-adrenergic agonist UX -14304 and compared with cisapride. In rats, both VB20B7 and cisapride enhanced gastric emptying of indigestible solids (steel spheroids) an d liquids (phenol red) at doses of 5-10 mg kg(-1) by mouth. Gastric em ptying of solid radiopaque markers in fasted beagle dogs was enhanced significantly by VB20B7 (0.25(-1) mg kg(-1) p.o.) whereas the effect o f cisapride (0.5-2 mg kg(-1) p.o.) did not reach statistical significa nce. Similar results were found when the radiopaque markers were given to the dogs following a standard solid meal The delayed gastric empty ing of indigestible solids and radiopaque markers by UK-14304 was reve rsed by oral administration of VB20B7 in both rats and dogs. Cisapride , however, was only effective in rats. In addition, gastric emptying o f a digestible solid/liquid meal was assessed by quantitating the rate of appearance of the radioactive markers in the duodenum of dogs. VB2 0B7 (0.2-1 mg kg(-1), i.v.) enhanced gastric emptying of both solid an d liquid phases while cisapride only enhanced emptying of the solid ph ase. The present study indicates that acute oral and intravenous admin istration of VB20B7 accelerates gastric emptying of both solids and li quids in different animal models.