Dopamine agonists in the treatment of
Parkinson's disease: past, present and future

by
Sit SY.
Bristol-Myers Squibb Pharmaceutical Research Institute,
5 Research Parkway, Wallingford,
CT 06492-7660, USA.
sits@bms.com
Curr Pharm Des. 2000 Aug;6(12):1211-48


ABSTRACT

An attempt is made by the author to highlight the important events that laid the foundation of dopamine agonists as a treatment strategy for Parkinson s disease. This debilitating neurodegenerative disorder is long recognized as a result of progressive cell loss in the substantia nigra of the midbrain. The destruction of dopaminergic neurons with projections to the striatum results in the diminishing striatal dopamine levels. Anticholinergic drugs were once widely used to counteract the relative overactivity of cholinergic output from the basal ganglia and the strategy was only met with limited success. The discovery of dopamine depletion and the use of levodopa - a dopamine metabolic precursor, led the way to dopamine replacement therapy . The initial success with levodopa was soon overshadowed by the long-term side effects associated with levodopa. Many new drugs were developed with the hope to replace or strengthen the usefulness of levodopa. Apomorphine and ergot alkaloids have been around for some time; they are recently joined by newer dopamine agonists such as ropinirole and pramipexole. Each of these has its own characteristics and has occupied a place in the pharmacotherapy of Parkinson s disease. In this review older aporphines and ergot alkaloids are discussed first. More emphasis is directed to the side-effect profiles, metabolism and pharmacokinetics in terms of their unique chemical structures. The most recent agonists will be briefly discussed before we move on to the future - the future of emerging novel classes of promising dopaminergic agonists. .


L-DOPA
Rasagiline
Neuroprotection
MAO-b inhibitors/PD
The introduction of L-DOPA
Antioxidant strategies against aging
Anti-Alzheimer/anti-Parkinson's drugs
Rasagiline versus selegiline metabolites
Rasagiline/ anti-apoptotic bcl-2 gene family
Dual AChE and MAO inhibitors and Alzheimer's
Rasagiline v selegiline: neuronal survival effects
Rasagiline (Agilect) in early Parkinson's disease
History of levodopa and dopamine agonists in Parkinson's disease


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