Effect of pretreatment with tricresylphosphates and phenobarbital on the metabolism and toxicity of procaine in rats.

We examined the effects of pretreatment with phenobarbital and tricresylphosphates, TOCP and TCP, on the metabolism and toxicity of procaine in rats. A single administration of procaine at a dose of 250 mg/kg intraperitoneally to adult rats caused convulsion, however, phenobarbital (80 mg/kg intraperitoneally daily, 4 days) pretreatment protected against the toxicity or procaine. In contrast, pretreatment of rats with TOCP (10 mg/kg per os) or TCP (10 mg/kg per os) 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 mumole/g brain wet weight, respectively. Toxic effects of procaine were, therefore, concluded to be due to the accumulation of the drug in the brain.