Dual Use Research of Concern: Derivatives of 3-Quinuclidinyl Benzilate (Bz)

Abstract

SummaryDual 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.

Drugs as Chemical Weapons: Past and Perspectives

“…The incapacitating effect (ICt 50 ) for inhalation of BZ aerosol is about 170 mg·min/m 3 , and the lethal effect (LCt 50 ) is about 200,000 mg·min/m 3 (about 30 times more effective than SN). Several hundred structurally related glycolates were synthesised during the course of the research, including agents with an oily consistency that can induce percutaneous poisoning [ 43 , 44 ]. Due to its high efficacy and relatively simple production, BZ was introduced into the ordnance (around 1961) and produced in quantity totalling 50 tonnes for aerial cluster bombs.…”