Dopamine agonists in the treatment of Parkinson's disease - Past, present and future

An attempt is made by the author to highlight the important events that lai d 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 midbra in. The destruction of dopaminergic neurons with projections to the striatu m results in the diminishing striatal dopamine levels. Anticholinergic drug s were once widely used to counteract the relative overactivity of choliner gic output from the basal ganglia and the strategy was only met with limite d 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 t he hope to replace or strengthen the usefulness of levodopa. Apomorphine an d ergot alkaloids have been around for some time; they are recently joined by newer dopamine agonists such as ropinirole and pramipexole. Each of thes e has its own characteristics and has occupied a place in the pharmacothera py of Parkinson's disease. In this review older aporphines and ergot alkalo ids are discussed first. More emphasis is directed to the side-effect profi les, metabolism and pharmacokinetics in terms of their unique chemical stru ctures. The most recent agonists will be briefly discussed before we move o n to the future - the future of emerging novel classes of promising dopamin ergic agonists.