Anticonvulsant Actions of Anticholinergic Drugs in Soman Poisoning

Abstract

The acute effects of the organophosphorus cholinesterase inhibitor soman include hypersecretions, convulsions, and death. The purpose of this study was to evaluate the anticholinergic compounds aprophen, atropine sulfate, azaprophen, benactyzine, benztropine, biperiden, scopolamine HBr, and trihexyphenidyl for their efficacy in preventing soman-induced hypersecretions and convulsions. Male rats were injected with the oxime HI-6 (125 mg/kg, i.p.), to increase survival time, along with various intramuscular doses of the anticholinergics 30 min prior to a dose of soman (180 micrograms/kg, s.c.; equivalent to 1.6 x the median lethal dose) that produced 100% convulsions. Signs of intoxication as well as the time-to-onset of convulsions were observed. The calculated anticonvulsant median effective dose values were 0.18, 0.33, 0.36, 0.55, 2.17, 2.30, 2.45, and 31.09 mumol/kg for scopolamine HBr, biperiden, trihexyphenidyl, benactyzine, benztropine, azaprophen, aprophen, and atropine sulfate, respectively. The same rank order of potency for inhibition of hypersecretions among these compounds was observed. Parallel studies with quaternary analogs of atropine sulfate and scopolamine HBr demonstrated, however, that these charged compounds afford no protection against soman-induced hypersecretions and convulsions. The results indicate that tertiary anticholinergic compounds afford protection against soman-induced convulsions and hypersecretions and that the beneficial anticonvulsant effects are mediated through the central cholinergic system. Excitatory amino acid neurotransmitter systems may be involved in the effectiveness of these compounds.

A Method for the Analysis of Tabun in Multisol Using Gas Chromatographic Flame Photometric Detection

“…Because the toxicity of GA is a frequently used reference in research to develop medical countermeasures to chemical warfare nerve agents, we sought a suitable solvent substitute for saline in the preparation and analysis of stable GA solutions. We chose Multisol as a substitute for saline because it was used previously to prepare anticholinergic, 17,18 anticonvulsant, 15,18,19 and GA solutions 16 that were stable and suitable for research. We confirmed the stability results 16 and extended the shelf life of GA in Multisol to fourteen months.…”

Scopolamine Antagonizes the Lethal Effects of O-isobutylS-2-(DIETHYLAMINO)ETHYL-methylphosphonothioatc (VR)

“…Notwithstanding, the use of scopolamine in medical management of OP toxicities pales in comparison to atropine despite evidence that seemed to suggest that scopolamine may be a more effective antidote than atropine (e.g., Anderson et al, 1994;Bertram et al, 1977;Capacio and Shih"1991;Harris et al, 1991;1994;Lennox et al, 1992;Janowsky et al, 1984;Jovic and Milosevic, 1970;Leadbeater et al, 1985;McDonough and Shih, 1993;Solana et al, 1991;Wescoe et al, 1948;Wills, 1963). In addition to its general antidotal effects, research from this institute Harris et al, 1994) has shown that scopolamine appeared to be a notably more powerful anticonvulsant than benzodiazepine derivatives (such as diazepam and midazolam) in animals intoxicated by soman (an extremely toxic chemical warfare agent).…”

Qualitative GC-MS Assessment of TCP and Tamorf Elimination in Rats

“…However, standard treatment leaves much to be desired since none of the standard oximes can be regarded as a universally suitable reactivator of AChE. In case of soman poisoning, reinhibition of AChE is faster than reactivation, and oxime therapy is ineffective due to the "aging" of the enzyme, which makes reactivation impossible (2,(10)(11)(12)(13).…”