Effect of chlorpheniramine on muricide induced by thiamine deficiency: pharmacokinetic and behavioral studies

Abstract

Chlorpheniramine (5-10 mg/kg) showed a dose-dependent suppressive effect on muricide induced by thiamine deficiency at 1 hr after oral administration. The ED50 value for muricidal suppression was about 7.1 mg/kg (95% confidence limits, 5.4-9.3 mg/kg). The maximum effect of muricidal suppression lasted for 1-2 hr after oral dosage (10 mg/kg). Chlorpheniramine was detectable at 10 min in the blood and brain of thiamine deficient killer-rats by using a high-performance liquid chromatographic method. Maximum brain and blood levels of chlorpheniramine appeared at 45 and 60 min, respectively. In terms of regional distribution, the highest levels were measured in the limbic system, especially in the hippocampus. Although neither blood nor brain levels of chlorpheniramine reflect its pharmacological activity, it can easily enter the brain and suppress muricide more potently than imipramine.