Twenty-five years of amantadine therapy in Parkinson's disease

Until a few years ago, the anti-parkinsonian effect of amantadine hydrochloride (AHCl) and amantadine sulfate (AS) could not be explained. The beneficial effect of amantadine, which has been observed for a long time, may be connected with its site of action at the glutamatergic excitatory transmitter system, i.e. the N-methyl-D-aspartate receptor. A clear distinction can be made between AHCl and AS with regard to this pharmacokinetic profile. Therefore, AS can be administered in higher doses than AHCl and is thus more effective. A major advantage of AS is that it can also be given intravenously. Yet so far it is marketed only in twelve countries of the world. Intravenous infusions of AS permit the treatment of patients with aphagia during akinetic crises and when L-dopa and dopaminergic agonists are not tolerated in the akinetic terminal stage. Amantadine has the best ratio of therapeutic effects to side effects when compared with the other anti-parkinsonian drugs currently used. Long-term treatment with amantadine may have a considerable L-dopa saving effect. Given in higher doses, amantadine may permit a drastic reduction of L-dopa dosis and dopaminergic agonists so that the well known side effects of such drugs disappear. In addition, some authors assume a neuroprotective action of amantadine. Unlike L-dopa and dopaminergic agonists, AS does not produce hemiballism or dystonia.