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 cm2 kg-1; 60 micrograms 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 LD50 of soman (100% mortality was recorded in the control group). Combining transdermal PHY with Scopoderm provided full protection against 1.5 LD50 of soman (protection of 70% against 3 LD50). When the prophylactic treatment was combined with post-exposure therapy (atropine, 10 mg kg-1; toxogonin, 10 mg kg-1) 1 min after 5 LD50 of soman, protection of 90% of the animals was achieved.
Meshulam
Y
Y
Department of Pharmacology, Israel Institute for Biological Research, Ness-Ziona.
Davidovici
R
R
Wengier
A
A
Levy
A
A
D000279:Administration, Cutaneous; D000818:Animals; D001923:Brain Chemistry; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D002802:Cholinesterases / Q000097:blood; D005260:Female; D006168:Guinea Pigs; D015918:Infusion Pumps, Implantable; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D010830:Physostigmine / Q000008:administration & dosage* / Q000032:analysis / Q000494:pharmacology; D011041:Poisoning / Q000517:prevention & control; D012601:Scopolamine / Q000008:administration & dosage* / Q000494:pharmacology; D012999:Soman / Q000008:administration & dosage / Q000506:poisoning*
D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D012999:Soman; D010830:Physostigmine; D012601:Scopolamine; D002802:Cholinesterases