Studies On The Sedation Of Gentianien And The Pharma Cokinetics In Vivo

Objective:To study the sedation and the mechanism of gentianine extracted from gentianae scabrae radix in rats; To study pharmacokinetic features of gentianine and if it can delivery across the blood-brain barrier.Methods:Clean mice were randomly grouped with the intraperitoneal injection of diffent doze of gentianine or physiological saline.After 30 min, injected the threshold dose of pentobarbital and the subthreshold dose of pentobarbita respectively to observe sleeping latency;sleeping durations;sleeping numbers.To detect the contents of GABA and 5-HT in brain of mice with the Mouse Gamma-aminobutyric acid,GABA ELISA kit and Mouse 5-Hydroxytryptamine,5-HT ELISA kit. Three groups of rats were treated by caudal vein injection of gentianine solution with different concentrations at 100 mg-kg-1,50 mg-kg-1,10 mg-kg-land the volume of 0.1 ml,then cut the tails at different time points,the blood was collected into centrifuge tube. The concentration of gentianine in serum was determined by HPLC. After rats were treated by a single intraperitoneal injection of gentianine solution,We performed a whole-body wash using 150ml of sterile isotonic saline injected into the right cardiac ventricle. Brains were aseptically removed and homogenized in isotonic saline. The concentration of gentianine was determined by HPLC.Results:1. Both the high and low dose group of gentianine can make the threshold dose of pentobarbital shorten sleep latency and extend sleep durations and can make the subthreshold dose of pentobarbital increased sleep numbers.2. GABA can be determined in brain of mice, and the contents increased with the intraperitoneal injection of gentianine dose and 5-HT also can be determined in brain of mice but its contents goes down when the intraperitoneal injection of gentianine dose increases.3. The pharmacokinetic procedure of gentianine given through intravenous injection could be described as opened two-compartment model.4. Gentianine can be determined in brain of rats, and the contents increased with the intraperitoneal injection of gentianine dose.Conclusion:1. Gentianine have the sedation effects and synergism by using with the Pentobarbital,it may be one of the anticonvulsant mechanisms.2. Gentianine can carry out its sedation effects by increasing the contents of GAB A and reducing the contents of 5-HT.3. Determined the pharmacokinetic model and obtained the main pharmacokinetic parameters. 4.Gentianine can delivery across the blood-brain barrier.