Effect of Pretreatment with Tricresylphosphates and Phenobarbital on the Metabolism and Toxicity of Procaine in Rats

Abstract

The effects of pretreatment with phenobarbital and tricresylphosphates, TOCP [triorthocresylphosphate] and TCP [tricresylphosphate], on the metabolism and toxicity of procaine in rats were examined. A single administration of procaine at a dose of 250 mg/kg i.p. to adult rats caused convulsion. Phenobarbital (80 mg/kg i.p. daily, 4 days) pretreatment protected against procaine toxicity. Pretreatment of rats with TOCP (10 mg/kg orally) or TCP (10 mg/kg orally) revealed a higher incidence of toxicity as compared to control rats. Mortality in procaine-treated rats was significantly decreased with phenobarbital-pretreatment and, conversely, increased with TOCP and TCP. Paralysis, convulsion and death were induced at the brain level of procaine of 0.303 .+-. 0.025, 0.480 .+-. 0.026 and 0.565 .+-. 0.018 .mu.mol/g brain wet wt, respectively. Toxic effects of procaine were due to the drug accumulation in the brain.