Organophosphorus Nerve Agents: Types, Toxicity, and Treatments

Abstract

Organophosphorus compounds are extensively used worldwide as pesticides which cause great hazards to human health. Nerve agents, a subcategory of the organophosphorus compounds, have been produced and used during wars, and they have also been used in terrorist activities. These compounds possess physiological threats by interacting and inhibiting acetylcholinesterase enzyme which leads to the cholinergic crisis. After a general introduction, this review elucidates the mechanisms underlying cholinergic and noncholinergic effects of organophosphorus compounds. The conceivable treatment strategies for organophosphate poisoning are different types of bioscavengers which include stoichiometric, catalytic, and pseudocatalytic. The current research on the promising treatments specifically the catalytic bioscavengers including several wild-type organophosphate hydrolases such as paraoxonase and phosphotriesterase, phosphotriesterase-like lactonase, methyl parathion hydrolase, organophosphate acid anhydrolase, diisopropyl fluorophosphatase, human triphosphate nucleotidohydrolase, and senescence marker protein has been widely discussed. Organophosphorus compounds are reported to be the nonphysiological substrate for many mammalian organophosphate hydrolysing enzymes; therefore, the efficiency of these enzymes toward these compounds is inadequate. Hence, studies have been conducted to create mutants with an enhanced rate of hydrolysis and high specificity. Several mutants have been created by applying directed molecular evolution and/or targeted mutagenesis, and catalytic efficiency has been characterized. Generally, organophosphorus compounds are chiral in nature. The development of mutant enzymes for providing superior stereoselective degradation of toxic organophosphorus compounds has also been widely accounted for in this review. Existing enzymes have shown limited efficiency; hence, more effective treatment strategies have also been critically analyzed.

Differential Impact of Severity and Duration of Status Epilepticus, Medical Countermeasures, and a Disease-Modifier, Saracatinib, on Brain Regions in the Rat Diisopropylfluorophosphate Model

“…Organophosphate nerve agents (OPNAs) have historically been used in chemical warfare scenarios to induce a variety of cholinergic symptoms (Coupland and Leins, 2005;Jett, 2007;Watson et al, 2015;Mukherjee and Gupta, 2020). OPNAs include the G-series, V-series, GV-series, and Novichek series (Mukherjee and Gupta, 2020).…”

“…Organophosphate nerve agents (OPNAs) have historically been used in chemical warfare scenarios to induce a variety of cholinergic symptoms (Coupland and Leins, 2005;Jett, 2007;Watson et al, 2015;Mukherjee and Gupta, 2020). OPNAs include the G-series, V-series, GV-series, and Novichek series (Mukherjee and Gupta, 2020). In 2013, Sarin, a G-series agent, was used as a chemical weapon and resulted in deaths and many with long term illness (Fields, 2017;John et al, 2018;Rodriguez-Llanes et al, 2018).…”

Saracatinib, a Src Tyrosine Kinase Inhibitor, as a Disease Modifier in the Rat DFP Model: Sex Differences, Neurobehavior, Gliosis, Neurodegeneration, and Nitro-Oxidative Stress

“…These agents have previously been used in chemical warfare scenarios, such as during the Iraq–Iran war and later in terrorist attacks, which suggests that they may be used in the future [ 1 , 2 , 3 , 4 , 5 , 6 ]. OPNAs include a wide array of molecules, including G-series agents such as Soman (GD), Sarin (GB), and cyclosarin (GF), V-series agents such as VX and VG, GV series, and Novichok [ 7 , 8 ]. These NAs cause cholinergic toxicity through the irreversible inhibition of acetylcholinesterase (AChE), accumulation of acetylcholine (ACh) at the synapses, and overactivation of ACh receptors [ 9 , 10 , 11 ].…”

FDA-Approved Oximes and Their Significance in Medicinal Chemistry

“…After the preliminary steps to counteract the OP poisoning, a second strategy will be to administer bioscavengers, either through aerosols or intravenously to purge the patient from the toxins. These bioscavengers are of three types, which include stoichiometric, catalytic and pseudocatalytic classes [44]. The stoichiometric category includes the single-use enzymes, while the catalytic group has a high turnover and can be divided into either mammalian and bacterial types, based on the source of the enzyme.…”