title: Effect of pretreatment with tricresylphosphates and phenobarbital on the metabolism and toxicity of procaine in rats.
abstract: 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.
mesh_terms: D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D003408:Cresols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004950:Esterases / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology*; D011343:Procaine / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D014317:Tritolyl Phosphates / Q000494:pharmacology*
chemical_list: D003408:Cresols; D014317:Tritolyl Phosphates; D011343:Procaine; D004950:Esterases; D010129:4-Aminobenzoic Acid; D010634:Phenobarbital