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Updated: Jun 23, 2026

Ole Isacson: Development of New Therapies for Parkinson's Disease
Published on: April 29, 2007
[Pharmacologic treatment of Parkinson disease]
1Department of Neurology, National Center Hospital of Neurology & Psychiatry, 4-1-1 Ogawahigashi-machi, Kodaira-shi, Tokyo 187-8551, Japan.
Abstract:
In this paper, I have discussed a modification in the current treatment strategy for Parkinson disease (PD) and the application of a new drug, zonisamide, for the treatment of PD. At the beginning of the 21st century, the following views were held strongly regarding the treatment of PD (1) L-dopa may be toxic, (2) dopamine agonist may exert neuroprotective effects, (3) dopamine agonists should be used as the initial treatment for parkinsonian patients without dementia or psychosis. However, the paradigm has now been modified to state (1) L-dopa does not accelerate disease progression, (2) no treatment modality exerts neuroprotective effects, (3) L-dopa is more effective than dopamine agonists in alleviating motor symptoms and improving the activities of daily living (ADL) score, in parkinsonian patients. Treatment with dopamine agonist is associated with fewer motor complications than L-dopa. Dopamine agonist therapy is associated with more frequent adverse events than L-dopa therapy, such as hallucinations and somnolence. There is no evidence of a long-term benefit with initial dopamine agonist therapy. Therefore, the treatment should be determined on a case-by-case basis. Furthermore, some clinical trials have indicated that early dopaminergic support for the degenerating dopaminergic system offers significant long-term clinical benefits for parkinsoninan patients. Zonisamide (25-50mg/day) improves motor functions and wearing-off without worsening dyskinesia in advanced cases of Parkinson disease. Furthermore, zonisamide affects an increases in the levels of glutathione and manganese superoxide dismutase expression and, it ameliorates reduction in the number of dopaminergic neurons in mice treated with 6hydroxydopamine (6-OHDA). Zonisamide may exert neuroprotective effects in parkinsonian patients.
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