Quisapride Hydrochloride

The objective of this study is to investigate the pharmacol. effects of 5-hydroxytryptamine 4 receptor agonist SHR116958 on its prokinetic activity with in vivo and in vitro animal models.Intestinal carbo medicinalis propulsion was performed in mice.Phenol red in mice was gastrically emptied.Fecal pellet was relieved.Twitch inhibition of SHR116958 was done in isolated whole ileum of guinea pigs.The results showed that the dose groups from 0.02 mg/kg^-1 to 0.20 mg/kg^-1 strikingly increased the rate of intestinal carbo medicinalis facilitation in one-month-old and three-month-old mice, resp. and increased the gastric emptying rate of phenol red in mice.Only SHR116958 2.0 mg/kg^-1 increased the output of fecal pellets in mice.In twitch inhibition in guinea pig ileum, groups which were only treated with SHR116958 and pretreated with drugs inhibiting enterokinesia like 5-hydroxytryptamine 4 receptor antagonist piboserod, μ receptor agonist morphine and M receptor antagonist atropine before being given SHR116958 decreased tension rates relative to those from pretreatment in a dose-dependent manner.It was concluded that the different doses of SHR116958 promoted gastrointestinal propulsion in a dose-dependent manner in mice.

A liquid chromatog.-tandem mass spectrometry (LC-MS-MS) method was successfully developed for the simultaneous determination of SHR116958 (a new gastroprokinetic agent) and its metabolite in rat blood plasma under the condition that tamsulosin was used as the internal standardThe analytes and internal standard were extracted by liquid-liquid extraction (LLE).After electrospray ionization, pos. ion fragments were detected in the multiple reaction monitoring (MRM) mode with a triple quadrupole tandem mass spectrometer.The method was linear in the concentration range of 2.71-5560 ng/mL^-1 with an average correlation >0.99 for both SHR116958 and its metabolite.Moreover, the method was validated according to FDA guidance in terms of accuracy and precision, in the meanwhile stability of compounds was well established in a battery of studies, i.e., bench-top, autosampler, and long-term storage stability as well as freeze/thaw cycles.Therefore, the method proved to be suitable for pharmacokinetics study of SHR116958 and its metabolite in rat.