THE EFFECT OF CHLORPROMAZINE ON THE TOXICITY AND BIOTRANSFORMATION OF PARATHION IN MICE

¹ Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania

The toxicity of oral parathion and paraoxon in mice was increased by 30 mg/kg of chlorpromazine (CPZ) injected i.p. one or six hours previously. The toxicity of these agents was reduced, however, when CPZ was administered one day previously. Hepatic microsomal and 900 x g supernatant fractions obtained from mice 24 hours after CPZ treatment converted more parathion to the active cholinesterase inhibitor, paraoxon, than did control preparations. One hour after CPZ this "activation" reaction was significantly inhibited. The detoxication of paraoxon by these liver fractions from mice given CPZ either one hour or one day earlier was not affected. The one-day pretreatment with CPZ had no effect on the inhibition of whole blood, red blood cell or plasma cholinesterase, but it reduced the inhibition of brain cholinesterase by parathion and paraoxon. This CPZ treatment did not affect the plasma levels of parathion, but the brain levels of parathion were significantly lowered. The protection by CPZ against the inhibition of brain cholinesterase by paraoxon suggests that paraoxon levels in brain are also lowered by CPZ. These findings are consistent with the conclusion that the protective effect of CPZ against the toxicity of parathion and paraoxon is due to decreased amounts of these agents in the brain.