Prophylactic transdermal treatment with physostigmine and scopolamine against soman intoxication in guinea‐pigs

This study was designed to evaluate the prophylactic efficacy of transdermally administered physostigmine (PHY) against soman exposure using guinea‐pigs. Transdermal PHY pad (3 cm 2 kg −1 ; 60 μg cm −2 ), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 h before exposure to the organophosphate. At the time of exposure, PHY concentrations in brain and plasma were ca. 3.6 ng g −1 and 4.1 ng ml −1 , respectively. Brain and whole blood cholinesterase (ChE) activity was inhibited to 70% and 47% of the original activity, respectively. Transdermal PHY by itself protected up to 70% of the animals exposed to 1.5 LD 50 of soman (100% mortality was recorded in the control group). Combining transdermal PHY with Scopoderm provided full protection against 1.5 LD 50 of soman (protection of 70% against 3 LD 50 ). When the prophylactic treatment was combined with post‐exposure therapy (atropine, 10 mg kg −1 ; toxogonin, 10 mg kg −1 ) 1 min after 5 LD 50 of soman, protection of 90% of the animals was achieved.