Abstract
The prophylactic efficacy of a combinational patch system containing physostigmine and procyclidine against soman intoxication was evaluated using dogs. Female beagle dogs (body weights 9–10 kg) were shaved on the abdominal side, attached with a matrix-type patch (7 × 7 cm) containing 1.5% of physostigmine plus 6% procyclidine for 2 days, and challenged with subcutaneous injection of serial doses (2–10 LD 50) of soman. Separately, in combination with the patch attachment, atropine (2 mg/dog) plus 2-pralidoxime (600 mg/dog) or atropine plus 1-[([4-(aminocarbonyl)pyridinio]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium (HI-6, 500 mg/dog) were injected intramuscularly 1 min after soman poisoning. The LD 50 value of soman was determined to be 9.1 μg/kg, and high doses (≥ 1.4 LD 50) of soman induced salivation, emesis, defecation and diarrhea, tremors and seizures, and recumbency of dogs, leading to 100% mortality in 24 h. The prophylactic patch, which led to mean 18.5–18.8% inhibition of blood cholinesterase activity by physostigmine and mean 7.9–8.3 ng/ml of blood concentration of procyclidine, exerted a high protection ratio (4.7 LD 50), in comparison with relatively-low effects of traditional antidotes, atropine plus 2-pralidoxime (2.5 LD 50) and atropine plus HI-6 (2.7 LD 50). Noteworthy, a synergistic increase in the protection ratio was achieved by the combination of the patch with atropine plus HI-6 (9 LD 50), but not with atropine plus 2-pralidoxime (5 LD 50). In addition, the patch system markedly attenuated the cholinergic signs and seizures induced by soman, especially when combined with atropine plus HI-6, leading to elimination of brain injuries and physical incapacitation up to 6 LD 50 of soman poisoning. Taken together, it is suggested that the patch system containing physostigmine and procyclidine, especially in combination with atropine and HI-6, could be a choice for the quality survival from nerve-agent poisoning.
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