Metrifonate: Update on a New Antidementia Agent

Objective: To review preclinical and clinical studies of metrifonate, a cholinesterase inhibitor relevant to the treatment of Alzheimer’s disease.

Data Sources: English-language literature identified by MEDLINE using the term metrifonate was reviewed, and bibliography-sorted searches were conducted.

Study Findings: Metrifonate is an organophosphate cholinesterase inhibitor effective in the treatment of the cognitive symptoms of Alzheimer’s disease and currently under review by the U.S. Food and Drug Administration. The active metabolite of metrifonate, 2,2-dimethyldichlorovinyl phosphate (DDVP), irreversibly inhibits the acetylcholinesterase enzyme. Although the elimination half-life of DDVP is 2-3 hours, the half-life of cholinesterase inhibition by DDVP is stable (26 days). Metrifonate can be administered once daily. Animal studies demonstrate its efficacy in enhancing memory in animals that have cholinergic deficits. Double-blind, placebo-controlled studies have shown the benefit of metrifonate compared with placebo in improving scores on the Clinical Global Impression of Change scale, the Alzheimer’s Disease Assessment Scale-cognitive subscale, and the Neuropsychiatric Inventory

Conclusion: Metrifonate is a useful addition to our limited armamentarium of agents helpful against the cognitive deficits of Alzheimer’s disease.