Citation

Fricke RF, Koplovitz I, Scharf BA, Rockwood GA, Olson CT, Hobson DW, Blank JA. Drug Chem. Toxicol. 1994; 17(1): 15-34.

Affiliation

Drug Assessment Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD.

Copyright

(Copyright © 1994, Dekker)

DOI

10.3109/01480549409064044

PMID

8168431

Abstract

Tacrine (THA) was evaluated in vitro and in vivo as a pretreatment for nerve agent intoxication. In vitro experiments showed that the primary effect of THA was direct inhibition of purified fetal bovine serum acetylcholinesterase (AChE) with a slight effect on slowing the aging rate of nerve agent-inhibited AChE. THA produced significant behavioral effects at doses above 1.7 mg/kg, i.m., in the mouse and 3.4 mg/kg, i.m., in the guinea pig. At the no observable effect level (NOEL) for mice (1.7 mg/kg), THA was effective (P < or = 0.05) in reducing tabun- and soman-, but not sarin-induced lethality in mice. Experiments in the guinea pig showed that at the NOEL (3.4 mg/kg, i.m.) THA was not effective in decreasing lethality due to soman exposure. Since there was significant overlap between pharmacologically effective doses of THA and those which produce behavioral toxicity, THA was not considered a suitable pretreatment for nerve agent intoxication.

Language: en