Alzheimer’s drug shows promise in treating nerve agent poisoning

The findings, published in the online edition of the Proceedings of the National Academy of Sciences, provide the basis for further development of a safe and effective treatment to protect people exposed to organophosphorus compounds, including nerve agents that have been used in chemical warfare and terrorist attacks, as well as pesticides used in households and on farms worldwide.

The study found that galantamine, a drug originally extracted from snowdrop flowers currently approved to treat Alzheimer’s disease, could be used as an antidotal therapy to counteract the lethal effects of even the most deadly organophosphorus compounds.

“The only medication currently approved by the Food and Drug Administration to prevent the catastrophic effects of nerve agent poisoning does not protect the brain,” explained Dr Edson Albuquerque, professor and chair of the department of pharmacology & experimental therapeutics at the University of Maryland School of Medicine and principal investigator on the study. “This medication, pyridostigmine, doesn’t effectively cross the blood-brain barrier.”

Most animals treated with pyridostigmine and exposed to toxic doses of nerve agents survive when they receive a combination of other medications, including atropine, oximes and benzodiazepines. However, even with this drug cocktail, animals surviving the initial nerve agent exposure can develop neurological effects.

Dr Albuquerque and his colleagues studied the effects of galantamine in an animal model to counteract the neurological devastation caused by nerve agents and organophosphorus pesticides.

In the study, those animals treated with galantamine and later exposed to lethal doses of soman or sarin survived and showed no signs of the most common symptoms of exposure to nerve agents, such as convulsions, respiratory distress and loss of coordinated movement. Comparatively, those animals treated with the standard therapy of atropine and benzodiazepines died after exposure.

The researchers repeated the experiments with paraoxon, the active metabolite of the insecticide parathion, and again, all of the animals survived with no signs of toxicity.

As it is difficult to predict when a person might be exposed to toxic levels of nerve agents on the battlefield or in a terrorist attack, or to toxic levels of insecticides during farm and garden work, the researchers also studied whether treatment with galantamine following exposure could counteract their toxicity effectively.

“All the animals treated with the antidotal therapy consisting of galantamine and atropine within five minutes after an exposure to lethal doses of soman and paraoxon survived with no side effects,” said Dr Albuquerque.

He says these findings have a clear relevance for military personnel under the threat of exposure to the deadly nerve agents and, as importantly, for the general population.