Methamidophos causes acute
cholinergic toxicity in several species, including man, and
organophosphate-induced delayed
polyneuropathy which has been reported in man but not in the hen.
Acetylcholinesterase (AChE) and
neuropathy target esterase (NTE) are thought to be the molecular targets of acute and delayed toxicity, respectively. The rate constants of inhibition (ka) and reactivation (k + 3) of human and hen brain AChE and NTE by
methamidophos resolved optical isomers are here reported. NTE inhibition was progressive and irreversible. Human and hen NTE ka (M-1.m-1) for D-(+)
methamidophos was 88 and 59, respectively, and for L-(-)
methamidophos 3.2 and 3.0, respectively. AChE spontaneously reactivates after inhibition. D-(+)
methamidophos 10(-3).ka (M-1.m-1) for human and hen AChE was 0.24 and 0.13; 10(3).k+3 (m-1) was 0.83 and 0.69, respectively. L-(-)
Methamidophos 10(-3).ka (M-1.m-1) for human and hen AChE was 5.7 and 2.8, whereas 10(3).k+3 (m-1) was 6.50 and 1.52, respectively. L-(-)-Inhibited AChE reactivated to about 60% for human and 30% for hen
enzymes, respectively. D-(+)-Inhibited AChE reactivated to about 10-20% for both species. Maximal reactivation occurred within 4-6 h when a plateau was reached. The larger and faster reactivation of human AChE inhibited in vitro by L-(-)
methamidophos suggests that a corresponding effect might be possible in vivo and therefore explain, in part, the relatively higher susceptibility of man to delayed
polyneuropathy induced by racemic
methamidophos which occurs, however, with doses always causing severe
cholinergic toxicity.