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THE U.
Phone: (818) 355-1568
THE U.S. ARMY MEDICAL RESEARCH AND DEVELOPMENT COMMAND HAS THE RESPONSIBILITY FOR DISCOVERING AND DEVELOPING PHARMACEUTICALS THAT WILL PROTECT THE SOLDIER AGAINST NERVE GAS AGENTS THAT ARE A THREAT IN WARFARE. ONE CONCEPT UNDER CONSIDERATION CONSISTS IN ADMINSITRA TION OF A PROTECTIVE DRUG PRIOR TO A NERVE GAS CHALLENGE. THE PRETREATMENT DRUG HAS A PROPHYLACTIC ACTIVITY PROTECTING THE SUBJECT AGAINST THE HARMFUL EFFECTS OF THE GAS. THE CARBAMATE DRUG PYRIDOSTIGMINE IS NOW BEING INVESTIGATED FOR THIS USE. PYRIDOSTIGMINE, A QUATERNARY, PROBABLY ACTS BY TEMPORARILY BLOCKING PERIPHERAL CHOLINESTERASE. IT WOULD BE USEFUL TO HAVE A HIGH ACTIVITY, LOW TOXICITY PROPHYLACTIC DRUG THAT WILL ACT IN THE CENTRAL NERVOUS SYSTEM AS WELL AS PERIPHERALLY, AS AN ALTERNATIVE TO PYRIDOSTIGMINE. THE DRUGS IN THIS PROJECT ARE DESIGNED TO PENETRATE INTO THE CNS WHERE THEY CAN PROVIDE ADDED PROTECTION AGAINST NERVE GAS AGENTS. FOUR NEW CARBAMATE TARGET CANDIDATES WILL BE SYNTHESIZED AND TESTED FOR PROTECTIVE ACTION AGAINST A CHALLENGE TO ACETYLCHOLINESTERASE BY AN ORGANOPHOSPHOROUS SUBSTRATE. HIGH PERFORMANCE LIQUID CHROMATOGRAPHY WILL BE USED TO MONITOR THE PROTECTIVE ACTION OF THE DRUG ON THE ENZYME. AN INHIBITION OF THE HYDROLYSIS OF THE SUBSTRATE BY THE ENZYME WILL INDICATE POTENTIAL IN VIVO PROPHYLACTIC ACTIVITY FOR THE NEW DRUG.
* Information listed above is at the time of submission. *