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Medicinal Chemistry Reviews - Online (Discontinued)

Editor-in-Chief

ISSN (Print): 1567-2034
ISSN (Online): 1567-2034

Organophosphate Induced Delayed Polyneuropathy

Author(s): Milan Jokanovic, Melita Kosanovic and Petar V. Stukalov

Volume 1, Issue 2, 2004

Page: [123 - 131] Pages: 9

DOI: 10.2174/1567203043480377

Price: $65

Abstract

This review discusses current understanding of organophosphate induced delayed polyneuropathy (OPIDP) with emphasis on molecular mechanisms, pathogenesis and possibilities for prevention / therapy. OPIDP is a rare toxicity caused by certain organophosphorus compounds (OP) characterized by degeneration of some long axons in the central and peripheral nervous system that appear about 2-3 weeks after exposure. The molecular target for OPIDP is considered to be an enzyme in the nervous system known as neuropathy target esterase (NTE). NTE can be inhibited by two types of inhibitors: a) phosphates, phosphonates, and phosphoramidates, which cause OPIDP when > 70% of the enzyme is inhibited, and b) phosphinates, carbamates, and sulfonyl halides, which inhibit NTE and cause either protection from or promotion of OPIDP when given before or after a neuropathic OP, respectively. The ability of a NTE inhibitor to cause OPIDP, besides its affinity for the enzyme, is related to its chemical structure and residue left attached to NTE. If such residue can undergo the aging reaction i.e. the loss of alkyl group bound to the enzyme, those OPs usually have high potency to cause OPIDP. Protection from neuropathic doses of OP inhibitors is obtained when NTE is inhibited with nonageable inhibitors. Promotion of OPIDP involves another site besides NTE because it might occur when all NTE is affected. It is now known that this other site is similar to NTE in that it is also sensitive to mipafox but at much higher concentrations. Promotion affects either progression or expression of OPIDP after the initial biochemical effect on NTE. There were some recent observations that development of OPIDP in hens can be influenced by atropine, oximes and methylprednisolone when they are given before or soon after neuropathic OPs.

Keywords: organophosphorus, organophosphates, nervous system, organophosphate induced delayed polyneuropathy


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