The Protection of Animals Against Organophosphate Poisoning by Pretreatment with a Carbamate. Gordon, J. J., Leadbeater, L., and Maidment, M. P. (1978). Toxicol. Appl. Pharmacol. 43 , 207–216. A number of carbamates of widely differing structure and toxicity have been tested for their ability (in conjunction with supporting treatment with atropine and an oxime, P2S) to protect guinea pigs against soman poisoning. There was no correlation between the protective activity of the carbamates and either their chemical structure or toxicity, suggesting that many factors (such as rates of absorption, distribution, metabolism, etc.) are involved in determining their protective action in addition to their ability to inhibit tissue acetylcholinesterase reversibly. The four most effective carbamates (pyridostigmine, mobam, physostigmine, and decarbofuran), which raised the LD50 of soman by a factor of about 8, were studied in more detail. The dose of carbamate was not critical, the protection being essentially constant for doses ranging from half to four times the maximum sign-free dose. The duration of the protective action of a single im injection of the carbamates was greater than 2 hr, pyridostigmine being the longest acting. Carbamate pretreatment in conjunction with therapy with atropine and P2S protected guinea pigs against poisoning by sarin, tabun, or VX. In the absence of the supporting therapy the guinea pigs were not sensitized to organophosphate poisoning by pretreatment with a carbamate. There were marked species differences in the response to the protection afforded by carbamate pretreatment against organophosphate poisoning: Guinea pigs responded better than rabbits, whereas rats were virtually unresponsive.