Amantadine is an old, antiviral compound, which moderately improves motor behavior in Parkinson's disease. Its current resurgence results from an innovative, delayed uptake and extended release amantadine hydrochloride capsule, given at bedtime once daily. It is the only approved compound for reduction of involuntary movements, so called dyskinesia, in fluctuating orally levodopa treated patients. It additionally ameliorates 'OFF' intervals characterized by impaired motor behavior. These beneficial effects result from higher and more continuous brain delivery of amantadine. Future clinical research is warranted on preventive effects of this amantadine capsule combined with enzyme blockers of central monoamine oxidase B and peripheral catechol-O-methyltransferase on motor complications in orally levodopa treated patients, as all these pharmacological principles support the concept of continuous dopamine substitution.
Keywords: Parkinson's disease; amantadine; dyskinesia; extended release; levodopa; motor complications; off periods.
Lay abstract Parkinson's disease (PD) is a common neurodegenerative disease. It causes motor and non-motor symptoms and provides considerable burden on the healthcare system. Levodopa is looked upon as gold standard therapy for PD. However prolonged administration and high dosing leads to the emergence of motor complications, which are involuntary movements, so called dyskinesia, and ‘OFF’ episodes. These are intervals with temporary onset of motor symptoms. The old, antiviral compound amantadine also moderately improves motor behavior in PD. Its current resurgence results from an innovative, delayed uptake and extended release amantadine hydrochloride capsule. It is given at bedtime once daily. This formulation provides a higher and more continuous brain delivery of amantadine. This new formulation improved motor complications in two Phase III studies. These benefits remained over long-term application. This formulation was well tolerated. No new safety concerns were observed (Table 1). This review suggests a future clinical study on preventive effects of this amantadine capsule combined with enzyme blockers of central monoamine oxidase B and peripheral catechol-O-methyltransferase in Parkinson's disease patients with a need for oral levodopa treatment. All these pharmacological principles support the concept of continuous dopamine substitution.