Medical Defense Against Nerve Agents: New Directions

Abstract

In spite of approximately forty years of international research by some of the world's leading scientists, chemical warfare remains a serious threat. Progress in medical defense against chemical warfare agents has been limited by disagreement concerning sites and mechanisms of action of the anticholinesterase nerve agents. Although it has been demonstrated that acute nerve agent toxicity is mediated through a loss of central respiratory drive, medical doctrine for nerve agent therapy continues to stress treatment of peripheral signs and symptoms, often with little regard for these agents' central nervous system actions. Recent technological advances have provided means of identifying the microscopic sites and mechanisms of action of both nerve agents and potentially useful drugs for medical chemical defense. A growing recognition of the significance of these compounds' direct actions upon excitable tissue, receptors and associated ionic channels, as opposed to enzymatic effects, is causing a re-examination of theoretical assumptions concerning nerve agent actions. Recognition of potential decrements in various aspects of military performance, as a consequence of the use of drugs for medical chemical defense, has resulted in greater emphasis on comprehensive behavioral screening of the effect that candidate drugs have on military performance. These recent developments are being exploited for novel approaches to medical chemical defensive systems which will be maximally effective in terms of prevention of chemical casualties, and minimally debilitating in terms of mission accomplishment.