Such efforts are important, they say, because of the war with Iraq and fears of possible chemical terrorism.

"Centrally active cholinesterase inhibitors, which block breakdown of the neurochemical acetylcholine are used therapeutically to treat Alzheimer's disease," said Dr. David Janowsky, professor and former chair of Psychiatry at the UNC School of Medicine. "Cholinesterase inhibitors in higher or more potent doses, such as VX, sarin and soman, have been developed for purposes of warfare as nerve agents."

Evidence indicates that such nerve agents are lethal, in part due to increasing acetylcholine in the brain, Janowsky said. Death from high-dose nerve agents occurs via seizures, as well as effects on the heart and lungs.

"The usual treatment for nerve agent toxicity is atropine plus a cholinesterase re-activator," he said. "In previous publications, we have shown in mice that the centrally acting anti-motion sickness agent scopolamine, which blocks the effects of acetylcholine in low doses, is markedly more effective than atropine, which does not affect the brain, in antagonizing the central effects of up to six times the lethal dose of physostigmine, the prototypic nerve agent and cholinesterase inhibitor.

Other studies have shown that low-dose physostigmine, given as pre-treatment, is effective against more powerful and tenacious nerve agents."

New experiments Janowsky and UNC colleague Dr. David Overstreet have conducted demonstrated that the popular anti-Alzheimers drug donezepil (Aricept) is effective in decreasing the actions of the irreversible nerve agent-like cholinesterase inhibitor DFP on rats body temperature,
'"/>

Contact: David Williamson
919-962-8596
University of North Carolina at Chapel Hill
24-Mar-2003