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 the strong cholinesterase inhibitor chlorpyriphos (organophosphate) and the weak cholinesterase inhibitors (donepezil, metoclopramide, and diphenhydramine) in different concentrations was evaluated. The protective ability of each one of the weak cholinesterase inhibitors alone and with a combination of two of them against the inhibitory action of chlorpyriphos was also detected. The results showed different patterns of inhibition depending on the inhibitor and its concentration when used alone or within a combination. When testing the protective ability, the results differed for each one of the inhibitors and for the combinations, depending on its own ability to bind the cholinesterase. Donepezil showed no ability to protect the enzyme against chlorpyriphos, but caused further increase in the inhibition when used alone or in combination. Diphenhydramine could have affinity to bind the enzyme more than metoclopramide and donepezil when used in combination against chlorpyriphos toxicity, and metoclopramide had higher affinity to inhibit erythrocyte cholinesterase in combination more than diphenhydramine and donepezil . The use of weak cholinesterase inhibitors alone or in combination may reduce the toxicity of organophosphates depending on the inhibitor used , but still not to a significant extent.

Keywords

• weak cholinesterases inhibitors
• chlorpyriphos
• donepezil
• metoclopramide
• diphenhydramine
• protection against organophosphates