Vol 6 n° 3 - Parkinson's disease
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arkinson’s disease (PD) is the second most com- mon neurodegenerative disease, affecting some 30 million patients  worldwide. Like Alzheimer’s  disease  (AD), it affects the elderly and causes considerable disability and suffering. The role of dopamine (DA) as a brain neuro- transmitter was discovered in the 1960s, and it was noted that there was a loss of this substance in specific brain areas in PD, which was linked to degenerative changes in the sub- stantia nigra,where DA cell bodies are located.This opened the door to the modern treatment of PD.The identification of DA as a key neurotransmitter in the extrapyramidal sys- tem and its depletion in PD rapidly resulted in a revolution in the treatment of PD and some related disorders. Levodopa The introduction of dihydroxyphenylalanine (levodopa) to the treatment of PD was a major scientific and clinical breakthrough in the treatment of this devastating disease. 3 1 5 P h a r m a c o l o g i c a l   a s p e c t s P Copyright © 2004 LLS SAS.  All rights reserved www.dialogues-cns.org Drug treatment of Parkinson’s disease Amos D. Korczyn, MD, MSc Parkinson’s disease (PD) is a common neurodegenerative disease. While its cause remains elusive, much progress has been made regarding its treatment. Available drugs have a good symptomatic effect, but none has yet been shown to slow the progression of the disease in humans. The most efficacious drug is levodopa, but it remains unclear whether the symp- tomatic benefit is associated with neurotoxic effects and long-term deterioration. The long-term problem associated with levodopa is the appearance of dyskinesias, which is significantly delayed among patients treated with dopamine ago- nists as initial therapy. Less clear is the role of other drugs in PD, such as monoamine oxidase inhibitors (MAOIs), includ- ing selegiline and rasagiline, the putative N-methyl-D-aspartate (NMDA) receptor antagonists amantadine and meman- tine, and the muscarinic receptor blockers. All these may be used as initial therapy and delay the use of dopaminergic drugs, or can be added later to reduce specific symptoms (tremor or dyskinesias). Advanced PD is frequently associated with cognitive decline. To some extent, this can be helped by treatment with cholinesterase inhibitors such as rivastig- mine. Similarly, hallucinations and delusions affect PD patients in the advanced stages of their disease. The use of clas- sical neuroleptic drugs in these patients is contraindicated because of their extrapyramidal effects, but atypical drugs, and particularly clozapine, are very helpful. The big void in the therapy of PD lies in the more advanced stages. Several motor symptoms, like postural instability, dysphagia, and dysphonia, as well as dyskinesias, are poorly controlled by exist- ing drugs. New therapies should also be developed against autonomic symptoms, particularly constipation.   © 2004, LLS SAS Dialogues Clin Neurosci. 2004;6:315-322. Keywords:  Parkinson’s disease; treatment; levodopa; COMT inhibitor; dopamine agonist Author affiliations: The Sieratzki Chair of Neurology, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel Address for correspondence: Amos D. Korczyn, MD, MSc, Sieratzki Chair of Neurology, Sackler School of Medicine, Tel-AvivUniversity, &Ramat-Aviv 69978, Israel (e-mail: neuro13@post.tau.ac.il)