Anticonvulsant and sedative effect of Fufang Changniu pills and probable mechanism of action in mice

Purpose: To investigate the anticonvulsant and sedative effects of Fufang Changniu Pills (FCP) and its probable mechanism of action in mice. Methods: The water decoction of FCP was prepared and the main constituents were determined by high performance liquid chromatography (HPLC). The anticonvulsant activities of FCP were evaluated by maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in mice. Pentobarbital sodium-induced sleeping time and locomotor activity measurements were performed to evaluate the sedative effects of FCP in mice. Finally, PTZ-induced chronic seizures were established, and expressions of gamma-aminobutyric acid A receptor (GABA-A) and glutamic acid decarboxylase 65 (GAD65) in the brains of the mice were assayed by western blot in order to explore the probable mechanisms of action of the drug. Results: Gallic acid, liquiritin, cinnamyl alcohol, cinnamic acid and glycyrrhizic acid were detected in FCP decoction. FCP (50, 100 and 200 mg/kg) showed significant anticonvulsant and sedative effects on epileptic mice induced by MES (p < 0.05) and PTZ (p < 0.05). Moreover, pentobarbital sodium-induced sleeping time and locomotor activity tests showed that FCP possesses sedative effect (p < 0.05). Western blot data indicate that FCP significantly up-regulated GABA-A and GAD 65 in the brains of chronic epileptic rats (p < 0.05). Conclusion: FCP has significant anticonvulsant and sedative effects, and the mechanism of its action may be related to the up-regulation of GABA-A and GAD 65 in mice brain.

Efficacy and Safety of Orally Administered Intravenous Midazolam Versus a Commercially Prepared Syrup

Background: Among different categories of sedative agents, benzodiazepines have been prescribed for more than three decades to patients of all ages. The effective and predictable sedative and amnestic effects of benzodiazepines support their use in pediatric patients. Midazolam is one of the most extensively used benzodiazepines in this age group. Oral form of drug is the best accepted route of administration in children. Objectives: The purpose of this study was to compare the efficacy and safety of a commercially midazolam syrup versus orally administered IV midazolam in uncooperative dental patients. Second objective was to determine whether differences concerning sedation success can be explained by child‘s behavioral problems and dental fear. Patients and Methods: Eighty eight uncooperative dental patients (Frankl Scales 1,2) aged 3 to 6 years, and ASA I participated in this double blind, parallel randomized, controlled clinical trial. Midazolam was administered in a dose of 0.5 mg/kg for children under the age 5 and 0.2 mg/kg in patients over 5 years of age. Physiologic parameters including heart rate, respiratory rate, oxygen saturation and blood pressure were recorded. Behavior assessment was conducted throughout the course of treatment using Houpt Sedation Rating Scale and at critical moments of treatment (injection and cavity preparation) by North Carolina Scale. Dental fear and behavioral problems were evaluated using Child Fear Schedule Survey-Dental Subscale (CFSS-DS), and Strength and Difficulties Questionnaire (SDQ). Independent t-test, Chi-Square, and Pearson correlation were used for statistical analysis. Results: Acceptable overall sedation ratings were observed in 90% and 86% of syrup and IV/Oral group respectively; Chi-Square P = 0.5. Other domains of Houpt Scale including: sleep, crying and movement were also not significantly different between groups. Physiological parameters remained in normal limits during study without significant difference between groups. Conclusions: “Orally administered IV midazolam” preparation can be used as an alternative for commercially midazolam syrup.