Mechanism of Action of Organophosphorus and Carbamate Insecticides

Abstract

Organophosphorus and carbamate insecticides are toxic to insects and mammals by virtue of their ability to inactivate the enzyme acetylcholinesterase. This review addresses the mechanism of inhibition of acetylcholinesterase by organophosphorus and carbamate esters, focusing on structural requirements necessary for anticholinesterase activity. The inhibition of acetylcholinesterase by these compounds is discussed in terms of reactivity and steric effects. The role of metabolic activation or degradation in the overall intoxication process is also discussed.

Carboxylesterases in the Metabolism and Toxicity of Pesticides

“…The mechanism of acute toxicity of carbamate insecticides is similar to that of OP insecticides, that is, inhibition of AChE activity at the cholinergic synapses (Fukuto 1990; Thompson and Richardson 2004). The mechanism of inhibition is similar to that proposed for hydrolysis and involves carbamylation of the nucleophilic serine, followed by release of an alcohol leaving group (Sogorb and Vilanova 2002).…”

Acetylcholinesterase and Acetylcholine Receptors: Brain Regional Heterogeneity

“…These authors suggested that mAChRs and nAChRs, as well as NMDA receptors, seem to play major roles in anticholinesterase-induced neurotoxicity and that combined treatment with cholinergic and NMDA antagonists might be beneficial in anticholinesterase-induced poisonings (Dekundy et al, 2001(Dekundy et al, , 2003. In similar studies, another NMDA receptor antagonist memantine, in combination with atropine, has been found equally effective against organophosphate and carbamate poisoning (Gupta, 1994;Gupta and Kadel, 1989, 1990, 1991a, 1991bMcLean et al, 1992).…”

“…Inhibition occurs as a result of phosphorylation of the serine (S 200 ) included in the catalytic triad of the active center by the organophosphate (Aldridge, 1950;Fukuto, 1990). Although this inhibition is usually considered irreversible, some reactivation of phosphorylated acetylcholinesterase can occur slowly as a result of hydrolytic cleavage, if the process of aging is not complete (Sultatos, 1994(Sultatos, , 2006.…”

“…The inhibition of AChE by an organophosphate is a function of both binding affinity at the active site and the rate of phosphorylation (Main, 1964). As a result, the bimolecular rate constant that can be determined experimentally continues to be considered the single best approach to compare the inhibitory power of various organophosphates (Fukuto, 1990;Mortensen et al, 1998). This strategy, however, depends upon the assumption that these in vitro reactions approximate first-order conditions because the oxon concentrations are much higher than the uninhibited enzyme.…”

Evaluation of the Acute Toxicity of Profenofos and Its Effects on the Behavioral Pattern of Fingerling Common Carp (Cyprinus carpio L., 1758)

“…In the absence of acetyl cholinesterase, acetylcholine level increased resulting in the failure of transmission of stimuli to the nerves or organs. This leads to the abnormal functioning of the body including loss of balance, moving in circular form (convulsions) and at higher concentrations of insecticides resulting in death of the organism (Fukuto 1990). Profenofos reduced the acetyl cholinesterase (Ach E) activity by 83% in the head of Eastern rainbow trout (Melanotaenia duboulayi) and 90% in the head and gills of Tilapia (Oreochromis mossambicus) (Kumar and Chapman 1998;Venkateswara et al 2003).…”