In vitro inhibition of human blood cholinesterases and protection against chlorpyriphos (organophosphate) by weak anticholinesterase drugs

Abstract

In vitro inhibition of human plasma and erythrocyte cholinesterase activities by thestrong cholinesterase inhibitor chlorpyriphos (organophosphate) and the weakcholinesterase inhibitors (donepezil, metoclopramide, and diphenhydramine) indifferent concentrations was evaluated. The protective ability of each one of the weakcholinesterase inhibitors alone and with a combination of two of them against theinhibitory action of chlorpyriphos was also detected. The results showed differentpatterns of inhibition depending on the inhibitor and its concentration when usedalone or within a combination. When testing the protective ability, the results differedfor each one of the inhibitors and for the combinations, depending on its own abilityto bind the cholinesterase. Donepezil showed no ability to protect the enzyme againstchlorpyriphos, but caused further increase in the inhibition when used alone or incombination. Diphenhydramine could have affinity to bind the enzyme more thanmetoclopramide and donepezil when used in combination against chlorpyriphostoxicity, and metoclopramide had higher affinity to inhibit erythrocyte cholinesterasein combination more than diphenhydramine and donepezil . The use of weakcholinesterase inhibitors alone or in combination may reduce the toxicity oforganophosphates depending on the inhibitor used , but still not to a significant extent.