The objective of the present investigation was to assess the comparative efficacy of prophylactic treatment with
d-tubocurarine (d-TC) (0.075 mg/kg),
atropine sulfate (16 mg/kg), and
atropine methylnitrate (16 mg/kg), employed singly or in combination against the diisopropylphosphorofluoridate (
DFP)-induced
myopathy in rat.
DFP (1.5 mg/kg, s.c.) produced signs of
cholinergic toxicity with predominantly peripheral involvement manifest as severe muscle
fasciculations beginning within 5-7 min and persisting in excess of 4-6 h. Maximal muscle fiber
necrosis was observed within 24 h. Rats were protected against the apparent behavioural and morphological changes as well as electrophysiological signs of neuromuscular toxicity by all pretreatment agents. Combined pretreatment with d-TC (0.075 mg/kg, s.c.) and
atropine methylnitrate (16 mg/kg, s.c.) was found to be most effective in attenuating
DFP-induced muscle fiber
necrosis as evidenced by complete absence of lesions and the prevention of
DFP-induced hyperactivity in nerve and muscle. Significant protection was afforded by all pretreatment agents when given alone. It is suggested that the pretreatment agents act presynaptically by preventing
drug-induced backfiring and muscle
fasciculations possibly by reducing the release of
acetylcholine (ACh). The
protective drugs in the concentrations used had no significant effect on the normal characteristics of conduction and transmission.