Amantadine in the Treatment of Parkinson's Disease

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

“…However, the future of this approach is in doubt due to the lack of effectiveness and the appearance of unexpected side effects in large controlled clinical trials (Freed et al, 2001;Olanow et al, 2003). Similar to the general approach, there is significant interest in the use of stem cells 1879 Charcot describes evidence that 'atropine' induces symptomatic relief of parkinsonism Charcot (1879) 1911 First synthesis of D/L Dopa Funk (1911) 1912 First description of Lewy bodies in the brain of Parkinson's disease patients Lewy (1912) 1940 First series of neurosurgeries of the basal ganglia to treat movement disorders Meyers (1940) 1950s First use of synthetic anticholinergic drugs for the treatment of Parkinson's disease Fahn (1989) 1951 First evidence for high concentrations of 'encephalin' (now referred to as dopamine) in the human striatum Raab and Gigee (1951) 1957 First evidence that L-DOPA reverses parkinsonian symptoms in animals treated with reserpine Carlsson et al (1957) 1958 First use of chemical assay to demonstrate high concentrations of dopamine in the brain Carlsson et al (1958) 1960 First evidence for striatal dopamine deficiency in Parkinson's disease Ehringer and Hornykiewicz (1960) 1961 First evidence that low doses of L-DOPA administered 'intravenously' have antiparkinsonian effects Birkmayer and Hornykiewicz (1961) 1962 First evidence that 'oral' low doses of L-DOPA have antiparkinsonian effects Barbeau et al (1962) 1967 First evidence that large oral doses of D,L-Dopa induce marked improvements of parkinsonian symptoms Cotzias et al (1967) 1969 First evidence that amantadine is an effective treatment of PD symptoms Schwab et al (1969) 1974 First evidence that oral D2 dopamine receptor agonist (bromocriptine) has antiparkinsonian effects Calne et al (1974a, b) 1975 First evidence that the MAO-B inhibitor, L-deprenyl, has clinical efficacy in PD Kapp (1992) 1983 First detailed description of MPTP-induced parkinsonism in humans Langston and Ballard Jr (1983) …”

The History of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies

“…The history of amantadine is of interest because of its serendipitous discovery as an anti-Parkinsonian agent. Developed as an antiviral agent, it was used widely in nursing home populations, and Schwab noted its unexpected benefit on tremor, balance, and akinesia in both Parkinson's disease and postencephalitic parkinsonian patients (Schwab et al 1969). This agent has mild dopamine effects, likely due to inhibition of striatal synaptic dopamine reuptake so that more dopamine is left within the synapse to activate dopamine receptors.…”

Glutamate receptor antagonism: neurotoxicity, anti-akinetic effects, and psychosis

“…The only anti-glutamatergic drugs available for the treatment of Parkinson's disease are the non-competitive NMDA receptor antagonists amantadine and memantine, which have only moderate anti-akinetic efficacy compared to dopamimetic substances (Schwab et al, 1969). However, threshold doses of memantine producing mild anti-akinetic effects result in pharmacotoxic psychosis in an unexpectedly high proportion of patients .…”