Screening of O-ethyl O-4-nitrophenyl phosphoramidate (ENPP) for delayed neuropathic potential.

ABSTRACT

O-Ethyl-O-4-nitrophenylphosphoramidate is a short-acting anticholinesterase and a possible candidate for a prophylactic agent against nerve agents since human acetylcholinesterase inhibited by this agent undergoes rapid spontaneous reactivation which can be accelerated further, if necessary, by treatment with oximes. Doses of the agent > 1 mg/kg (s.c.) given to unprotected rats were fatal in a short time but 2 rats and one hen given 0.5 mg/kg survived. Hens given 2.5 or 4 mg/kg s.c. 20 min after prophylactic physostigmine + atropine survived acute effects and were killed 4.5 or 24 h later. Brain and spinal cord neuropathy target esterase levels of these hens were depressed only 4-10% compared with levels in brains from hens given only oxime + atropine or of undosed animals. Clinical signs of neuropathy were not seen in surviving birds observed for 3 weeks. It appears there would be negligible delayed neuropathic hazard associated with administration of O-ethyl-O-4-nitrophenylphosphoramidate at subacute doses.