Author: Sit, S.Y.

Source: Current Drug Metabolism, Volume 6, Number 12, 1 August 2000 , pp. 1211-1248(38)

Publisher: Bentham Science Publishers

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 Parkinsons 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 Parkinsons 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.

Keywords: Apomorphine; Parkinosons disease; Cerebrospinal fluid CSF; Ergot Alkaloids; Claviceps purpurea; Dopamine receptor; Parkinsonism; Aporphine; N norapomorphine; Morphine; Dopaminergic; Antinociceprive activity; Morphine alkaloids; Emetine alkaloids; Emetic activity; Lisuride; Cabergoline; Antihypertensive; Mesulergine; 5HT2 receptor antagonist; Hyperprolactinemia; Antiparkinsonian activity; Graphic analyses; Ropinirole; Pramipexole

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612003399581

Publication date: 2000-08-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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