Atropine and Other Anticholinergic Drugs

Abstract

Abstract : The nerve agents are highly toxic organophosphorous (OP) compounds. The agents of greatest concern, along with their chemical names and two-letter military designations, are tabun (o-ethyl N.N-dimethyl phosphoramidocyanidate; GA), sarin (isopropyl methylphosphonofluoridate; GB), soman (pinacolyl methylphosphonotluoridate; GD), cyclosarin (cyclohexyl methylphosphonofluoridate, GF), VX (o-ethyl S- 2-N,N- diisopropylaminoethyl methyl phosphonofluoridate) and a Russian V-type agent designated VR (0-isobutyl S-(2-diethylamino)ethyl methylphosphonothioate). The nerve agents inhibit the cholinesterase (ChE) family of enzymes that includes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). It is the inhibition of AChE, the enzyme that hydrolyzes the cholinergic neurotransmitter acetylcholine (ACh), that produces the toxic action of nerve agents. Inhibition of BChE activity by itself is not known to produce any toxic effect. Nerve agents bind to the active site of the AChE enzyme, thus preventing it from hydrolyzing ACh. The enzyme is inhibited irreversibly, and the return of esterase activity depends on the synthesis of new enzyme molecules ( 1% per day in humans). All nerve agents penetrate the central nervous system (CNS), with the G-type agents acting more rapidly centrally than the V-type.