A comparative study of blood changes and brain acetylcholinesterase inhibition by monocrotophos and its analogues in rats

The effects of monocrotophos and its newly synthesized analogues, RPR-II and RPR-V, on hematology and blood chemistry 24 hr post-treatment were studied in rats given doses of 0.96, 1.23, and 3.0 mg/kg po, respectively. It was found that monocrotophos caused a significant increase in the mean WBC count. RPR-V, a significant decrease in hematocrit and RBC count, whereas RPR-II did not alter any hematological parameter. The activities of membrane-bound enzymes in serum were not significantly changed by all three compounds except for a statistically significant increase of 38% in SGOT activity by RPR-II. Only monocrotophos caused a significant inhibition of the brain acetylcholinesterase activity. In vitro studies with partially purified preparations of rat brain cholinesterase revealed that monocrotophos was the most potent anticholinesterase agent, followed by RPR-II and RPR-V. All three compounds caused inhibition of rat brain cholinesterase by decreasing the Vmax and increasing the Km values, indicating a mixed type of inhibition. The two analogues appeared to be less neurotoxic than monocrotophos.