Metrifonate (Trichlorfon): a review of the pharmacology, pharmacokinetics and clinical experience with a new acetylcholinesterase inhibitor for Alzheimer’s disease

Abstract

Metrifonate is a cholinesterase inhibitor, effective in the treatment of both the cognitive and behavioural symptoms of Alzheimer’s disease (AD). Previously used as an antihelminthic and insecticide, clinical experience with metrifonate in AD patients is large and growing. The parent compound is relatively inactive; it is metabolised non-enzymatically to 2,2-dimethyl dichlorovinyl phosphate (DDVP), which irreversibly inhibits the acetylcholinesterase enzyme. The elimination half-life of DDVP is 2.1 h; cholinesterase inhibition by DDVP is stable and may persist for up to 55 days. Metrifonate can be administered once daily. In vitro and animal data regarding possible carcinogenesis of metrifonate and DDVP are conflicting; experience in the treatment of humans with schistosomiasis or AD support its safety. Animal studies demonstrate its efficacy in enhancing memory in animals with cholinergic deficits. Double-blind, placebo-controlled studies have shown the benefit of metrifonate compared to placebo in improving scores on the Clinical Global Impression of Change, Alzheimer’s Disease Assessment Scale-Cognitive Subscale and the Neuropsychiatric Inventory.

• acetylcholinesterase inhibition
• Alzheimer’s disease
• behavioural cognition
• DDVP
• dementia
• dichlorvos
• metrifonate
• trichlorfon