Chapter 68 - Pyridinium oximes in the treatment of poisoning with organophosphorus compounds

Abstract

Organophosphorus compounds (OPs) have been used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX, and others. Exposure to even small amounts of an organophosphorus compound can be fatal and death is usually caused by respiratory failure resulting from paralysis of the diaphragm and intercostal muscles, depression of the brain respiratory center, bronchospasm, and excessive bronchial secretions. The mechanism of OP poisoning involves phosphorylation of the serine hydroxyl group in the active site of acetylcholinesterase (AChE) leading to inactivation of this essential enzyme which has an important role in neurotransmission. AChE inhibition results in the accumulation of acetylcholine at cholinergic receptor sites, producing continuous stimulation of cholinergic fibers throughout the central and peripheral nervous systems. Presently, a combination of an antimuscarinic agent, for example, atropine, AChE reactivator, such as one of the recommended pyridinium oximes (PAM-2, TMB-4, HI-6, LüH-6), and diazepam are used for the treatment of organophosphate poisoning in humans. In this chapter we review the mechanisms of action of OP and the role of pyridinium oximes used as AChE reactivators in the treatment of OP poisonings.