Influence of Alpha-Chloralose on Muscle Relaxant Effect of Chlorzoxazone in Rats and Pharmacodynamic Analysis

抄録

The Pharmacological response intensity of chlorzoxazone (CZX) was measured by the crossed extensor reflex (CER) method in anesthetized rats. The appropriate dose of alpha-chloralose (ACH) was examined to bring about a quantitative effect of CZX. The pharmacodynamics of CZX was also characterized in the anesthetized rats at three different doses of CZX. When rats were anesthetized with ACH at three different doses (80, 110, and 150 mg/kg i.p.), the CER response caused by CZX at the doses of 25, 50, and 75 mg/kg p.o. was depressed dosedependently. Among these three different doses of ACH, 80 and 110 mg/kg gave similar results in describing the pharmacological response induced by CZX with time, whereas a dose of 150 mg/kg of ACH elicited a stronger and longer CZX response than the other two doses. The area under the intensity-time curve also showed the same tendency. These findings suggested that the dose size ranging from 80 to 110 mg/kg of ACH for surgical anesthesia was appropriate to evaluate the quantitative pharmacological response of CZX. Pharmacodynamic analysis offered the results that the dose-normalized biophase levels of CZX were coincident with each other when CZX was given at three different doses under ACH anesthesia at the dose of 80 mg/kg. This suggested that the disposition of CZX in rats obeyed linear kinetics and the theoretical values of CZX-induced response would be predictable. This implied that pharmacological response intensity of CZX was reasonably related to the relative biophase CZX level via Hill's equation.