Evaluating Response to Metrifonate

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Metrifonate, administered orally to patients with probable Alzheimer’s disease in a oncedaily dose, readily enters the brain and inhibits brain acetylcholinesterase (AChE) activity in a dosedependent fashion. Metrifonate is a prodrug, converted non-enzymatically to 2,2-dichlorovinyl dimethyl phosphate, a long-acting inhibitor of AChE that produces stable enzyme inhibition over time. In combination, these pharmacologic characteristics lead to a reduced side effect profile in comparison with several other cholinesterase inhibitors. Both preliminary and confirmatory pivotal studies have shown that significant cognitive improvement is achieved with this medication in comparison with placebo in patients with probable Alzheimer’s disease. Moreover, these studies also have demonstrated that metrifonate benefits the global function—a measure comprising domains of cognition, function, activities of daily living, and behavior—of patients with Alzheimer’s disease. The medication is generally well tolerated, and no significant laboratory abnormalities occur. Therefore, metrifonate is a useful treatment for the symptoms of Alzheimer’s disease.

J Clin Psychiatry 1998;59(suppl 9):33–37