Amantadin - Klassische Indikationen und das antivirale Potenzial in Zeiten von COVID-19

Antiparkinsonian activity of amantadine was first described in 1969 and was confirmed by several trials in later years. The improvement of parkinsonian symptoms is mild. However, in patients with motor fluctuations a clear reduction of dyskinesia and akinetic crisis could be observed. A possible neuroprotective impact is still under discussion, but lacking evidence. Moreover, amantadine is efficient in the treatment of disorders of vigilance, chronic fatigue (e. g. multiple sclerosis), tardive dykinesia and neurolepticas induced extrapyramidal motor symptoms. The clinical efficacy is caused by manifold mechanism of action. Initially, enhancement of dopaminergic transmission has been observed after amantadine and considered main mechanism of action. Currently, several direct targets are likely such as: (1) aromatic aminoacid decarboxylase, (2) Sigma-1 receptors, (3) nicotinergic receptors, (4) phosphodiesterase, (5) GDNF (glial-cell-derived neurotrophic factor). Dose dependently, there are also other probable targets like NMDA antagonism, serotoninergic-5-HT3 antagonism and potassium channel blockade. Preclinical data suggest an association of both neuroprotective potential and antidyskinetic properties with the antiglutamatergic activity of amantadine. Since the COVID- 19 pandemic, the antiviral efficacy of amantadine generated increasing interest. Several in vitro studies detected inhibition of SARS-CoV-2 virus. These results could support clinical renaissance of this drug in the coming years.