Prophylaxis and the mechanism for the initiation of organophosphorous compound-induced delayed neurotoxicity.
Recent work concerned with the mechanism underlying the development of organophosphorous compound-induced delayed neurotoxicity (OPIDN) is reviewed. Topics covered include the prophylaxis of OPIDN by phenylmethylsulfonyl fluoride and other agents, neurotoxic esterase (NTE) as measured using either labelled di-isopropyl phosphorofluoridate or an esterase assay, and the relationship between NTE and the development of OPIDN. There is considerable evidence that NTE has the biochemical properties which should be expected for the initiation site for OPIDN. However, the in vitro assays as currently performed may not entirely reflect the behavior of organophosphorous compounds in vivo, or the assays may not be sensitive enough to identify the actual target. It is argued that prophylaxis is a distinguishing characteristic of OPIDN which is not necessarily related to NTE inhibition, although it does provide evidence that NTE is involved. It is concluded that the NTE hypothesis could be furthered by additional studies with peripheral nerve, more sensitive methods for the detection of potential binding sites, and the establishment of a physiological role for NTE which relates it to the neuropathy.
Carrington
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Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
D000818:Animals; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D013997:Time Factors
D009943:Organophosphorus Compounds