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

Incapacitating Agents“Biotechnology: Impact on Biological Warfare andBiodefense.” 85 They warned that weapons designers ofthe future will be able to engineer agents that producea range of effects “…including death, incapacitation,neurological impairment.” The former Soviet biologicalweapons effort, ostensibly halted as early as 1992,included programs to develop “bioregulators” asweapons to replace classical chemical weapons. Somechemical warfare watchers are very concerned aboutthe growing interest in such substances. The followingexcerpts are illustrative:There is concern over the potential use of bioregulatorsas weapons in warfare or by terrorists. A paperin late 2001 stated that these organic compounds “…are capable of regulating a wide range of physiologicactivities…” and if used as weapons “… could potentiallycause profound systemic effects on multipleorgan systems.” 85(p3) . . .Bioregulators of concern discussed in the paper includedcytokines, eicosanoids, neurotransmitters,hormones, and plasma proteases. Neurotransmittersmediate chemical transmission in the nervous systemthrough their interactions with specific receptors. Inthe central nervous system these neurotransmitterreceptorinteractions have a major role in regulatingconsciousness, mood, anxiety, perception, and cognition.86Bioregulators have sometimes been referred to as“calmatives,” and some writings list as calmativescompounds that do not produce this outcome. Theterm has also been used by the Russians in referringto the drug (or drugs) used in the Moscow theaterrescue in 2002. Most therapeutic drugs that relieveanxiety or produce some kind of sedation, includinganxiolytics such as diazepam, antipsychotic neurolepticssuch as chlorpromazine, muscle relaxants,and sedative-hypnotic drugs have been placed in thisartificial category.Also included in the category are serotonin 5-HT 1areceptor agonists and selective serotonin reuptakeinhibitors, of which fluoxetine (Prozac, Eli Lilly, Indianapolis,Ind) is perhaps the most familiar. A profusionof these “biochemical” antidepressants have emergedon the psychiatric market since Prozac was released in1987. From a pharmacological standpoint, it seems inappropriateto call them calmatives. As antidepressantsthey tend to produce increased energy, even thoughinitial use may sedate some patients, especially thosesuffering from insomnia. Their therapeutic effectsmay be delayed by days to weeks. They all possesshigh safety margins, but their potential effectivenessas incapacitating agents is questionable.Some researchers suggest that α-2 adrenergic agonistsshould also be classified as calmatives. Clonidine,the most familiar drug of this type, is effective in verylow dosage and used to lower blood pressure or tohelp in the stabilization of hyperactivity in children.Although potent and able to produce sedation, clonidinewould be a highly dangerous drug to use in thefield because life-threatening hypotension can developafter even small multiples of the therapeutic dose.The opioids can also be found in the calmative category,as can exotic drugs such as D 3dopamine agonistsand cholecystokinin-B antagonists. Pramipaxole, a D 3dopamine agonist, is useful in treating the symptomsof Parkinson’s disease, and as little as 0.125 mg supposedlyhelps to control restless legs syndrome. It hasalso been used to treat compulsive gambling. Antagonistsof cholecystokinin-B (the brain counterpart of thestomach hormone gastrin) can potentiate the analgesiceffects of other drugs and lower body temperature undercertain conditions. Corticotropin-releasing factorantagonist is a hypothalamic hormone. It stimulatesthe release of adrenocorticotropic hormone from thepituitary gland. How an antagonist to this hormonewould serve any useful purpose as a calmative isunclear.The calmatives group has come to include not onlythe neuropeptides and neuromodulators but manypreexisting drug families long recognized by pharmacologiststo be distinctly different in their effects. Oftenbelladonnoid drugs (such as BZ) or scopolamine, formerlymarketed as Sleep-Eze (Whitehall Laboratories,New York, NY), an over-the-counter bedtime sedative,are barely mentioned. Sleep-Eze was a popular drugamong people with insomnia until it was taken offthe market because of concerns about potential abuse.Sominex (JB Williams Company, Cranford, NJ), Sleep-Eze, and Unisom (Pfizer Consumer Healthcare, NewYork, NY) are now over-the-counter drugs containingdiphenhydramine (an antihistamine) instead ofscopolamine as their active ingredient. Both antihistaminesand cannabinoids have also been ignored bythe calmative classifiers.From a purely practical standpoint, administeringsome of the candidates with larger molecules byaerosol, or even via ingested food or water, is difficultto imagine. Not only are many neuropeptides quitelarge, consisting of long chains of amino acids, butthey would also be extremely difficult to disseminatein the field. Even if they reach the lungs or digestivetract, they would ultimately be obliged to cross theblood–brain barrier, a difficult task for many complexmolecules.Pharmaceutical companies are currently developingmethods to ferry or “piggyback” hormones, antibodies421