Ligustrazine Enhances the Hypnotic and Analgesic Effect of Ketamine in Mice

The purpose of this study was to determine the effects of different concentrations of ligustrazine, an extract from Chinese herb, on ketamine requirement for hypnosis and analgesia in mice. In the hypnotic response study, mice were randomly allocated to receive saline or ligustrazine at 10, 20, 40, 80 or 160 mg·kg^-1 by intraperitoneal injection. Ketamine was administrated 15 min after ligustrazine injection. The hypnotic response was determined by assessing loss of the righting reflex (LORR) after ketamine injection. The dose of ketamine was determined by modified Dixon's up-and-down method in each group. In the analgesia study, different doses of ligustrazine were administrated 15 min before 50 mg·kg^-1 ketamine injection. The analgesia effects (pain threshold) were determined by heat radiation-induced tail-flick latency and evaluated before ligustrazine administration or 5, 15, 30 and 60 min after ketamine administration. The ED₅₀ [95% confidence interval (CI)] for hypnosis induced by ketamine was 54.1 (44.8, 65.3) mg·kg^-1. Ligustrazine dose-dependently decreased the ED₅₀ for ketamine to induce hypnosis, which was [31.6 (26.2, 38.1)] mg·kg^-1 with the addition of 80 mg·kg^-1 ligustrazine and [27.7 (22.6, 33.7)] mg·kg^-1 with the addition of 160 mg·kg^-1 ligustrazine, respectively (p<0.05). Ligustrazine at 160 mg·kg^-1 also increased pain threshold in the presence of ketamine. Ligustrazine enhanced the hypnotic effect of ketamine in a dose-dependent manner. Ligustrazine at a large dose also increased the analgesic effect of ketamine.