CHAPEL HILL – Because of concerns about terrorists one day using such deadly nerve agents as sarin, soman, tabun and VX, a University of North Carolina at Chapel Hill scientist is urging the government and medical researchers to investigate potentially more effective treatments.
Dr. David S. Janowsky says he has a strong candidate drug that might prevent many deaths from an attack.
Studies he and colleagues published 16 years ago suggest scopolamine, a drug already routinely used to combat motion sickness, could be a significant improvement over the standard treatment, atropine, in treating civilians and military personnel exposed to toxic nerve agents.
Janowsky is professor and former chair of psychiatry at the UNC School of Medicine and former director of the Center for Alcohol Studies. A report on his previous experiments and his views appeared in the Lancet, a widely read British medical journal in late January.
“Standard treatment for nerve agent poisoning includes supportive measures combined with atropine and a compound called pralidoxime,” Janowsky said. “In animals, however, atropine’s effectiveness in treating high doses of nerve agents is doubtful because atropine has only weak effects on the central nervous system and it is in the brain that high doses of nerve agents cause death due to convulsions. Atropine is unlikely to work any better in human beings for the same reason.”
The earlier experiments involved laboratory mice. When exposed to varying concentrations of physostigmine, a potent chemical affecting nerve function, significantly more mice survived if they were given scopolamone alone or that compound plus methscopolamine than if they received atropine, he said.
For example, 90 percent of mice exposed to 2.25 milligrams of physostigmine per kilogram of body weight survived if they were treated with 0.2 milligrams of scopolamine per kilogram of body weight, compared with only 18 percent of exposed mice given the same amount of atropine, the physician said. None given only a salt solution survived.
At six milligrams of physostigmine per kilogram of body weight -- a significantly higher dose that would kill all untreated mice six times over, atropine did not boost survival at all. By contrast, 71 percent of mice given scopolamine and 85 percent of mice given scopolamine plus methscopolamine survived.
“At relatively low but lethal doses of physostigmine, which is a reversible centrally acting cholinesterase inhibitor that can serve as a prototypical nerve agent, scopolamine and atropine had about the same effect,” Janowsky said. “At higher doses scopolamine was much more effective.”
In the early 1980s, the UNC scientist performed his research on physostigmine not because of concern about nerve gases but because of an interest in depression, which tiny amounts of the compound produce, he said. Scopolamine appears to reverse physostigmine toxicity quickly in poisoned animals by acting much more on the brain and central nervous system than atropine does. It has the same effect as atropine on the rest of the body.
In high doses, physostigmine has the same deadly effects as nerve agents.
“I wrote the new paper because no one seems to have picked up on the suggestion that scopolamine might work better than atropine does against nerve agents and because the threat of a nerve agent attack has intensified recently,” Janowsky said. “It is definitely worth further investigation.
Right now in emergency rooms they are using a drug that is unlikely to work well in many people following a serious attack.”
Scopolamine already is available in many emergency rooms for other reasons but has not been evaluated for use against nerve agents, he said. A report in the medical literature from the early 1970s described the case of a person accidentally poisoned by a nerve agent and treated successfully with scopolamine.
“We hope this will never need to be tested in humans, but if an attack comes against the military or civilians, unfortunately, we could have every opportunity to see if it works,” Janowsky said.
Nerve agents increase greatly a natural neurotransmitter compound in the body called acetylcholine, he said. Normally, acetylcholine causes a parasympathetic response. The heart slows, blood pressure drops, pupils constrict and the gastrointestinal tract becomes active. The neurotransmitter is the functional opposite of adrenalin, which generally revs up the body, causing a fight response.
Massive amounts of acetylcholine accumulate after nerve agent exposure causing breathing to become labored or stop and the heart to stop. Because of effects on the brain, seizures occur, and death can follow quickly.
Materials provided by University Of North Carolina At Chapel Hill. Note: Content may be edited for style and length.
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