Amantadine, an antiviral agent, was by chance found to have antiparkinsonism properties. Its mode of action in parkinsonism is unclear, but it may potentiate dopaminergic function by influ-encing the synthesis, release, or reuptake of dopamine. It has been reported to antagonize the effects of adenosine at adenosine A 2A receptors, which are receptors that may inhibit D2 receptor func-tion. Release of catecholamines from peripheral stores has also been documented.
Peak plasma concentrations of amantadine are reached 1–4 hours after an oral dose. The plasma half-life is between 2 and 4 hours, most of the drug being excreted unchanged in the urine.
Amantadine is less efficacious than levodopa, and its benefits may be short-lived, often disappearing after only a few weeks of treat-ment. Nevertheless, during that time it may favorably influence the bradykinesia, rigidity, and tremor of parkinsonism. The stan-dard dosage is 100 mg orally two or three times daily. Amantadine may also help in reducing iatrogenic dyskinesias in patients with advanced disease.
Amantadine has a number of undesirable central nervous system effects, all of which can be reversed by stopping the drug. These include restlessness, depression, irritability, insomnia, agitation, excitement, hallucinations, and confusion. Overdosage may pro-duce an acute toxic psychosis. With doses several times higher than recommended, convulsions have occurred.Livedo reticularis sometimes occurs in patients taking amanta-dine and usually clears within 1 month after the drug is with-drawn. Other dermatologic reactions have also been described. Peripheral edema, another well-recognized complication, is not accompanied by signs of cardiac, hepatic, or renal disease and responds to diuretics. Other adverse reactions to amantadine include headache, heart failure, postural hypotension, urinary retention, and gastrointestinal disturbances (eg, anorexia, nausea, constipation, and dry mouth).Amantadine should be used with caution in patients with a history of seizures or heart failure.