抄録
Organophosphorous (OP) compounds were discovered before World War II to be used as warfare agents. OPs obtained quickly important applications as agricultural insecticides, and are today most widely used pesticides. OPs can be divided into several classes, the toxicity of which markedly differs from each other. For example, the i.p. LD50 value of soman, an OP warfare agent, is about 100 µg/kg in rat, whereas the corresponding value for pure malathion, a common insecticide, is in gram range. Mechanisms of differences in the acute toxicity between OPs in not known, but there may be several reasons including affinity of the OP to an enzyme, acetylcholinesterase (AChE), that catalyzes the cleavage of acetylcholine (ACh), an important neuronal transmitter. OP-induced acute central nervous (CNS) system toxicity results in the accumulation of ACh due to AChE inhibition. Excess ACh leads, mainly via muscarinic receptor activation, to increased neuronal activation associated with increased phosphatidylinositol signaling, elevation of neuronal calcium, activation of protein kinase C, increased production of reactive oxygen metabolites, altered gene expression, activation of other excitatory neuronal pathways, and apoptotic or necrotic death of neurons. Signs of acute OP intoxication include cholinergic symptoms salivation, lacrimation, urination and defecation and tonic-clonic convulsions, respiratory depression, and death.
