Medical Aspects of Chemical Warfare (2008) - The Black Vault

Incapacitating AgentsSeveral other glycolates that were lower in potencybut shorter in duration than BZ received limitedtesting. 112–115 BZ has often been incorrectly described asfar stronger than LSD, and the reported “hundreds ofcompounds more potent than BZ”do not exist. 116 Afterthe BZ program ended, enhanced glycolate formulationsfor use as incapacitating agents were deemeddangerous to develop and, because of their perceivedslow onset time during evaluations, unsuitable formilitary use.Treatment StudiesThe ability to reverse the incapacitating effects ofbelladonnoids (or drugs such as LSD and opioids) is ofparamount importance, not only for the sake of the affectedindividual, but also in any operation that needsto preserve fighting strength. Given in doses abovetheir ID 50, belladonnoids, although eminently treatable,can be swift in action; a large number of troopsin a delirious state would pose a serious problem forcommanders. Fortunately in the case of BZ, during theonset and peak periods of drug action, somnolence (oreven coma) would keep individuals virtually immobilefor up to 24 hours—probably much longer with highdoses. This somnolent period would provide time toplace victims in a safe environment and treat themwith an anticholinesterase to prevent the emergenceof irrational behavior.For at least 24 hours, subjects incapacitated by BZshow little inclination, and are unable, to act aggressively.This placidity is a pharmacological phenomenon.Aggression in mouse-killing rats, for example,is inhibited completely by BZ-like drugs. These ratsotherwise attack and kill mice placed in their cagewithout delay. BZ and other belladonnoid agents couldlegitimately be called “calmatives.” Lack of in-depthunderstanding of the 2- to 3-day delay between onsetof delirium and partial recovery, which is the onlytime when behavior may become active and impulsive(though rarely aggressive), may have led to the conclusionthat BZ use would provoke mayhem.Before the mid 1960s, standard pharmacologicaltextbooks taught that no antidotes, including cholinesteraseinhibitors, were able to reverse belladonnoiddelirium. 117 However, in 1963, the antidotal effectivenessof physostigmine was rediscovered at EdgewoodArsenal 118 when Goodman located and translated an1864 report by an Austrian ophthalmologist on thesuccessful use of Calabar bean extract (the naturalsource of physostigmine). 117 The report recounted thestory of two prisoners who drank a quantity of tinctureof belladonna, thinking it was alcohol. The physiciancalled to attend them learned they had consumed belladonna,noted their saucer-like pupils, and suspecteddrug-induced delirium. 119 The doctor next reasonedthat, because a few drops of Calabar extract reversedenlarged pupils and the loss of near vision caused bythe belladonna drops he used for eye examinations,Calabar might have similar antidotal effects in thebrain. To the most affected prisoner he gave a smallamount of the extract in a spoonful of sugar and gaveonly plain sugar water to the other. Soon, the first manreturned to a lucid state, able to describe the theft of thebelladonna solution, while the second man remainedunchanged.Toward the end of the 1940s, perhaps seeking analternative to insulin coma, a small group of psychiatristsbegan to use atropine to produce coma inpsychiatric patients. 99–101 The physicians who introducedthis unusual form of pharmacotherapy, unlikethe authors of human pharmacology chapters at thetime, were evidently aware that physostigmine couldbring atropinized patients back to conscious awareness.They reported routinely administering 4 mg ofphysostigmine by injection soon after inducing a shortperiod of atropine coma.This useful finding received little attention frommainstream clinicians. The growing preference forneostigmine as treatment for such disorders as surgicalileus and myasthenia gravis had made physostigmineincreasingly obsolescent. Neostigmine was valuedfor its lack of central effects, but physostigmine easilyenters the brain and in fact may have been avoidedbecause of its potential central toxicity. Anticholinesterasecompounds other than physostigmine were alsostudied at the Edgewood clinical facility to determinetheir effectiveness as a BZ antidote. Even lethal nerveagents were evaluated as antidotes for BZ, 120,121 buttheir clinical application is highly impractical andinappropriate. Physostigmine was determined tobe the safest and most appropriate antidote for BZintoxication.Repeated injections of physostigmine in BZ-exposedindividuals, usually 2 to 4 mg at hourly intervals,maintained coherent speech and the ability to carryout tasks; without the physostigmine the individualswould have been continuously delirious for the next2 to 3 days. In both cases, NF test scores rose dramaticallywhen physostigmine was administered, revertedto an incapacitated level when physostigmine wastemporarily withheld, and responded again whentreatment was reinstituted.In 1967 Edgewood physicians had published thefirst double-blind controlled study demonstratingthe effectiveness of physostigmine in reversingscopolamine delirium. 118 Later they reconfirmed425