Residual behavioral incapacitation after therapy of soman intoxication: the effect of a soman simulator.

Abstract

When rats are intoxicated with high doses of the cholinesterase inhibitor soman (5-8 X LD50), the compound is temporarily stored in a "depot" from which it is gradually released. Thus, despite an initially successful therapy with the oxime HI-6 and atropine, the released soman re-intoxicates the organism and death may ensue in several hours. Soman simulators, i.e., non-toxic structural analogues of soman, have been synthesized which are capable of preventing death in soman poisoned rats by modifying the accumulation and release of soman from its depot. Earlier experiments have demonstrated that prophylaxis with the simulator pinacolyl dimethyl phosphinate (PDP) combined with HI-6 and atropine is capable of preventing death in animals heavily poisoned with soman. Moreover, gross observation of successfully treated animals suggested that they were in fairly good condition with respect to general health and neurological functioning. Since the degree of behavioral impairment remaining after soman intoxication and subsequent treatment may be a crucial factor for survival under difficult circumstances, quantitative behavioral experiments were carried out to substantiate these observational findings. Using a recently developed, tv/microprocessor-based system for the measurement of coordinated hindlimb movement in the rat, the residual behavioral effects of successful soman therapy were evaluated. Performance of animals treated with atropine sulphate (25 mg/kg, IP), soman (5 X LD50, IV), HI-6 (56 mg/kg, IV) and the soman simulator PDP was compared to that of animals similarly treated but without additional PDP treatment and to that of saline controls in a series of experiments, varying dose and time of injection of PDP.(ABSTRACT TRUNCATED AT 250 WORDS)