Effect of chlorpromazine pre-treatment on the inhibition of total cholinesterases and butyryl-cholinesterase in brain of rats poisoned by physostigmine or dichlorvos

Abstract

Pre-treatment of rats with chlorpromazine at a dose of 15 mg/kg i.p. 60 min before they were killed in potentiation of toxicity of physostigmine (0.5 mg/kg i.p., 20 min before killing) as evidenced by about a 2-fold increase in the inhibition of total ChE and BuChE in whole-brain preparations, as measured by a radio-isotope method. Chlorpromazine also enhanced the toxicity of dichlorvos (dimethyl-2,2-dichlorovinylphosphate) at a dose of 5 mg/kg i.p. 10 min before the rats were killed, but to a lesser extent than that of physostigmine, whereas it did not enhance it all when doses of dichlorvos (8 and 10 mg/kg) alone caused an inhibition of total ChE over 65%. Regarding the neurochemical mechanisms of potentiation of physostigmine effects by chlorpromazine, a study on discrete brain regions (cerebellum, medulla oblongata + pons, hypothalamus, striatum, midbrain, hippocampus, cerebral cortex) showed a considerable quantitative similarity of effects in various regions both as concerns total ChE and BuChE; potentiation of BuChE was slightly more pronounced than that of total ChE. Potentiation did not depend on possible antiChE effects of chloropromazine in vivo since the drug alone did not produce any inhibition of total ChE in whole brain and brain regions, and it produced only a slight inhibition of BuChE in the cerebellum, medulla oblongata + pons and midbrain, which could not explain the pronounced potentiation in all regions. The results suggest that the neurochemical mechanism of potentiation is not selectively linked to brain cholinergic systems but possibly linked to more general phenomena such as alterations in membrane permeability.