DUAL USE RESEARCH OF CONCERN: DERIVATIVES OF 3-QUINUCLIDINYL BENZILATE (BZ)

Summary Dual Use Research of Concern (DURC) deals with the unintended consequences of research and development and is particularly acute in the area of drug development. The United States National Science Advisory Board for Biosecurity (NSABB) has defined DURC as "research that, based on current understanding, can be reasonably anticipated to provide knowledge, products, or technologies that could be directly misapplied by others to pose a threat to public health, agriculture, plants, animals, the environment, or materiel” (1). One particular receptor antagonist and glycolate anticholinergic compound (BZ, QNB or 3 -quinuclidinyl benzilate) was stockpiled by the United States as a non-lethal chemical weapon that incapacitates and severely degrades the capability of exposed individuals (2). Given time and medical treatment, combatants and non-combatants exposed to such incapacitating agents could recover without any long-term effects. The purpose of this review is to identify potential new and more potent incapacitating agents based on the structures of BZ or atropine using peer reviewed publications of new pharmaceutical agents. A number of peer reviewed studies have reported on compounds with effects observed at lower concentrations than or comparable to BZ suggesting that these compounds could also be developed as potential chemical incapacitating chemical warfare agents and represent good examples of the principal of Dual Use Research of Concern.