Abstract
We examined the effects of pretreatment with phenobarbital and tricresyl-phosphates, 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 of 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 μmlole/g brain wet weight, respectively. Toxic effects of procaine were, therefore, concluded to be due to the accumulation of the drug in the brain.
