Differences in central and peripheral neural actions between soman and diisopropyl fluorophosphate, organophosphorus inhibitors of acetylcholinesterase

Abstract

Toxic doses of acetylcholinesterase (AChE) inhibitors produce prominent motor symptoms (fasciculations, fibrillations, and body tremors) and muscle fiber necrosis. The severity and quality of motor symptoms and fiber necrosis depend upon the specific AChE inhibitor. To examine the importance of nerve and muscle activity in producing muscle necrosis, we recorded electromyographic activity from normal and acutely denervated rat gastrocnemius muscle following administration of the organophosphorus AChE inhibitors soman and diisopropyl fluorophosphate (DFP). The motor symptoms induced on the denervated side represented activity originating at the nerve terminal while those of the contralateral nondenervated muscle represented the sum of peripheral plus central descending activity. The results indicate that soman and DFP produce different responses. At nonlethal toxic doses, the majority of motor symptoms induced by soman is due to impulses descending from the central nervous system, and a proportion of these symptoms are epileptiform activity. This activity is not generated at spinal levels. In contrast, DFP produces motor symptoms mainly by peripheral action that is dependent on a functioning nerve terminal. At lethal doses, both agents have central and peripheral effects. Different patterns of electrical activity are associated with each of the motor symptoms. We found that muscle fiber necrosis correlates best with peripherally generated high-frequency repetitive discharges.