l-Dopa has been the cornerstone of therapy in Parkinson's disease (PD) for 30 years. It is a precursor to dopamine, the primary neurotransmitter that is depleted in the disease. l-Dopa is taken up by surviving nigrostriatal neurons and converted to dopamine, which, in turn, can be stored and released. The continuous degeneration of these nigrostriatal neurons is at the heart of the occurrence of late complications of l-dopa therapy, particularly motor fluctuations and dyskinesia.<sup>16 Fabbrini G., Mouradian M.M., Juncos J.L. , et al. Motor fluctuations in Parkinson’s disease: Central pathophysiological mechanisms, part I Ann Neurol 1988 ;  24 : 366

Cliquez ici pour aller à la section Références</sup> Dopamine receptor agonists are drugs that bypass the degenerating neurons and directly stimulate the intact, although denervated, postsynaptic receptors in the striatum. This effect would be expected to provide an advantage for dopamine agonists over l-dopa, and thus increasing interest in these compounds has been at the center of PD clinical therapeutic research since the mid-1970s. In addition to that noted previously, there are other theoretical advantages to the use of dopamine agonists in PD.<sup>81 Stern M.B. Contemporary approaches to the pharmacotherapeutic management of Parkinson’s disease: An overview Neurology 1997 ;  49 (suppl 1) : S2

Cliquez ici pour aller à la section Références, 90 Watts R.L. The role of dopamine agonists in early Parkinson’s disease Neurology 1997 ;  49 (suppl 1) : S34

Cliquez ici pour aller à la section Références</sup> First, these drugs are not affected by similar pharmacokinetic shortcomings that are seen with l-dopa. That is, there is no competition for absorption in the gut with dietary neutral amino acids and no competition for penetration of the blood-brain barrier. Second, they have substantially longer elimination half-lives, which allows for more prolonged stimulation of receptors when compared with l-dopa. Third, there is no need for metabolism of these compounds into dopamine in the central nervous system as seen with l-dopa. Fourth, dopamine agonists can be used to target specific receptor subtypes so that they may possibly have more specific therapeutic effects and eliminate certain side effects. Fifth, dopamine agonists may also provide a wider therapeutic window with a decrease in risk of dyskinesias. Finally, these drugs may diminish the metabolism of dopamine and therefore decrease the formation of free radicals in the striatum.

Dopamine agonists have been used in the treatment of PD since 1974.<sup>64 Parkes D. Drug therapy: Bromocriptine N Engl J Med 1974 ;  301 : 873

Cliquez ici pour aller à la section Références</sup> In 1997, two new novel agents with differing receptor stimulating profiles from the early agonists were approved by the Food and Drug Administration, the first new agonists since 1989. Thus, four are now available in the United States for the treatment of PD patients (Figure 1). Although these drugs have expanded the role of dopamine agonists and certainly led to further improvement of PD disability and treatment, many unanswered questions remain. This article first discusses current knowledge of dopamine receptors, then reviews in detail the four drugs that are currently available in the United States; this is followed by a brief discussion of other important dopamine agonists that have received substantial press in the neurologic literature. Finally, some of the controversies are addressed.