Interactions between anticholinesterase agents and neuroleptics in terms of cholinesterase inhibition in brain and other tissues of rats

Abstract

Treatment of rats with chlorpromazine (CPZ, 15 mg/kg i.p. 60 min before sacrifice) did not modify cholinesterase (ChE) activity, but considerably enhanced the inhibition of total ChE induced by physostigmine (PhS, 0.5 mg/kg i.p. 40 min after CPZ) in brain, skeletal muscle, myocardium, lung, liver, and kidney. Additional experiments also showed a prolongation of PhS inhibition by CPZ in brain. The enhanced inhibition of total ChE due to CPZ depended in most peripheral organs on the effect on pseudoChE (as measured by a spectrophotometric method), except in the case of skeletal muscle in which potentiation of PhS effect was observed on true acetylcholinesterase (AcChE). The results indicate that the potentiation by CPZ of PhS inhibition occurs in all organs tested and is relatively non specific. CPZ was found to potentiate slightly the effects of Mevinphos but did not interact with Carbaryl, Diazinon or Azinphos. Furthermore, haloperidol did not potentiate the effects of physostigmine.