EFFICACY COMPARISON OF SCOPOLAMINE AND DIAZEPAM AGAINST SOMAN-INDUCEDDEBILITATION IN GUINEA-PIGS

The efficacy of diazepam (DZ) and scopolamine (SCP), in combination wi th atropine (ATR) + oxime therapy, against soman-induced seizure/convu lsive activity and associated brain damage has been demonstrated, but the efficacy of each against the incapacitating effects of soman has n ot been addressed. Thus, the therapeutic efficacies of SCP (5 doses; 0 -0.86 mg/kg) and DZ (5 doses; 0-5 mg/kg), when each was used in conjun ction with ATR (3 doses; 0.5-8 mg/kg) + 2-PAM (25 mg/kg) therapy, were compared in groups of pyridostigmine pretreated guinea pigs exposed t o 1.6, 2.0, 2.5, or 3.2 LD50s of soman. Response surface methodology w as employed to describe the relationship between soman-induced incapac itation and the ATR/DZ or ATR/SCP dosages. Incapacitation was measured by toxicity scores assigned by three graders to test animals at 60 mi n postsoman. Results show that as the dosage of SCP increased, the mea n toxicity scores decreased. Also, within the indicated dose ranges us ed, the efficacy of SCP was not dependent on the presence of ATR. In c ontrast, ATR alone was found to be more effective than when combined w ith DZ at any dose, and indicates that DZ might be temporarily contrib uting to soman-induced incapacitation. These findings suggest that in guinea pigs, SCP could replace ATR or DZ, or both, as therapy against soman-induced incapacitation. (C) 1994 Society of Toxicology.