ISSN:
1432-0738
Keywords:
Methamidophos
;
Pesticide
;
Phosphoramidates
;
Organophosphorus
;
Neuropathy target esterase (NTE)
;
Delayed neuropathy
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The interaction with neural neuropathy target esterase (NTE) and acetylcholinesterase (AChE) in vivo of methamidophos (O,S-dimethyl phosphorothioamidate), its resolved stereoisomers and five higher O-alkyl homologues has been examined along with the ability of these compounds to cause organophosphorus-induced delayed polyneuropathy (OPIDP) in adult hens. For the lower homologues AChE was more sensitive than NTE and it was impossible to achieve high inhibition of NTE in vivo without both prophylaxis and therapy against acute anticholinesterase effects; for then-hexyl homologue high inhibition of NTE could be achieved without obvious anticholinesterase effects and spontaneous reactivation of inhibited AChE was seen as in vitro. The maximum tolerated dose ofl(−) methamidophos or of the ethyl oriso-propyl homologues did not inhibit NTE more than 60%, and surviving birds did not develop OPIDP. Then-propyl,n-butyl andn-hexyl compounds caused typical OPIDP at doses causing a peak of 70–95% inhibition of NTE in brain, spinal cord and sciatic nerve soon after dosing. Racemic methamidophos caused unusually mild OPIDP associated with very high inhibition of NTE at doses estimated to be 〉8 times the unprotected LD50 and thed-(+) isomer caused OPIDP at about 5−7× LD50. Clinical effects correlated with histopathology in 19 out of 20 examined birds. In contrast to results of many previous studies with organophosphates and phosphonates, all these cases of OPIDP were associated with formation of inhibited NTE which could be reactivated ex vivo by treatment of autopsy tissue with KF solution. It is not clear whether “aging” of inhibited NTE had occurred but with less associated stabilisation of the enzyme-phosphorus bond or whether, even without aging, the unusual N-unsubstituted phosphoramidate caused sufficient disturbance in or near the NTE target to initiate the same degenerative process as that caused typically by generation of “aged” organophosphorylated NTE.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02098026
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