TABLE 8-1
Potential Antidotes for Nerve Agent Poisoning

Antidote	Efficacy	Availability	Potential Civilian Utility	Stockpile
Scopolamine	Poorly absorbed through inhalation	Yes	Yes	Hospitals, ED
Ipratropium Bromidea	A quaternary anticholinergic agent	Yes for inhalation	Yes	Hospitals, ED
3-quinuclidinyl benzilate (BZ, QNB)b	CNS effects	Withdrawn	None	N/A
N, N´ trimethylene bis (pyridine-4-aldoxime bromide) combined with benzactyzine	CNS effects Benzactyzine is a cholinolytic agent	Benzactyzine withdrawn	None	N/A
Benzodiazepines (Diazepam, Lorazepam, Midazolam)c,d	Controls seizures	Autoinjector: 10 mg/2-ml vials (convulsant antidote)	Field: yes Lorazepam preferred Base: no Intravenous preferred	Prehospital, Emergency, Hospitals Health Department
Pro-2-PAM (Dihydropyridine derivative)	Prodrug or drug carrier permits traversing blood brain barrier	Experimental	Inadequate evidence	N/A
Obidoxime (Toxogonin)	Effective in rodent model	European Countries	Inadequate evidence	N/A
H Series of oximes TMB4 (Hagedorn) (HI-6 compounds)e­h	Effective in rodent model Toxicity profile under study Direct central and peripheral anticholinergic activity	Stability in question	Inadequate evidence	N/A
Methanesulfonate salt of pralidoxime (P2S)		Standard in UK	Inadequate evidence	N/A
Nicotine hydroxamic acid methiodide (NHA)	Pretreatment of soman exposure in rhesus monkeys	Research potential		N/A
Monoisonitrosoacetone (MINA)	May have 48 hr post-exposure utility	Research potential		N/A
Butyryl cholinesterase (BChE)i­k (Human BChE Mutants)	Exogenous scavenger for highly toxic organophosphorus poisons. Equine BChE studied in rhesus monkeys	Human BChE available (? FDA status)	Prehospital: high-risk environment pretreatment essential personnel ED: no	N/A
Stoichiometric scavengers: acetylcholinesterasel,m and carboxylesterasen,o [fetal bovine products]	Binds broad spectrum of nerve agents Longer half-life Pretreatment common disadvantage that they have high MW and react 1:1 with organophosphates. Effective at 1:1 concentration.	Research	Prehospital: high-risk environment pretreatment essential personnel ED: no	N/A
Catalytic scavengers: Organophosphorus acid anhydride hydrolase,p,q [parathionase] modified AChE, modified BChE	Pretreatment: advantage small amount of effective enzyme to destroy large amounts of toxin.	Research	No	N/A
Catalytic monoclonal antibodiesr,s	Mice hybridomas secret monoclonal antibodies which hydrolyze phosphonates. The antibody is an IgG2a with Kappa light chain character with activity against soman, but there is no cross reactivity against sarin or tabun.	Rodent models		N/A
Reactive topical skin protectants	Protection against penetration and will detoxify nerve agents.	Animal model	Prehospital and ED personnel. Field use in high-probability zone	N/A
Memantinet	May be neuroprotective in cell culture for soman but severe injury still noted.	Antiparkinsonian agent	No evidence	N/A
Thienylcyclohexylpiperidine (TCP)u	Acts as a noncompetitive inhibitor of NMDA receptors. May prevent and interrupt soman-induced seizures. Better approaches available.	Experimental	No evidence	N/A
Dizocilpine (MK-801)v	Act as a noncompetitive inhibitor of (N-Methyl-D-Aspartate) NMDA receptor channel during seizures induced by soman in guinea pigs. Adverse effects similar to those of PCP.	Experimental	No evidence	N/A

^aGross, 1988; ^bWaelbroeck et al., 1991; ^cMartin et al., 1985; ^dMcDonough et al., 1989; ^eLundy et al., 1992;. ^fKoplovitz and Stewart, 1994; ^gWorek et al., 1995; ^hKassa, 1995; ⁱRaveh et al., 1993; ^jBroomfield et al., 1991; ^kMasson et al., 1993; ^lMaxwell et al., 1992.; ^mVelan et al., 1991; ⁿMaxwell et al., 1987; ^oDoctor et al., 1993; ^pLittle et al., 1989; ^qRay et al., 1988; ^rLenz et al., 1992; ^sLenz et al., 1984; ^tDeshpande et al., 1995; ^uCarpentier et al., 1994; ^vSparenborg et al., 1992.

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