Differentiation of dopamine agonists and their role in the treatment of Parkinson’s disease

Summary

Since the pioneering work of Hornykiewicz and his colleagues, it has been recognized that dopaminergic cells die selectively in Parkinson’s disease, and considerable improvement in symptoms can be achieved by administering levodopa, so that it may be converted to dopamine. However, levodopa has side-effects, and its duration of action is relatively brief. For these reasons, alternative approaches have been undertaken to stimulate the dopamine receptors. In particular, artificial agonists for dopamine receptors have been developed. The pioneer compound was bromocriptine, which stimulates the D2 family of receptors. Bromocriptine is an ergot derivative, and other compounds that are structurally related to ergot have been developed. In particular, lisuride and pergolide have been used for several years. Recently, an ergot derivative with an exceptionally long plasma half-life has been studied, cabergoline. Now there are also non-ergot derivatives that are D2 agonists, and are likely to have a role in the treatment of Parkinson’s disease. Both ropinirole and pramipexole fall into this category, and each has been released in various countries for the treatment of Parkinson’s disease. All of these compounds stimulate the D2 family of receptors, but they have varying actions on the D1 family of receptors. At present, there is no definite information on the role of the D1 family of receptors in either the therapeutic response to levodopa, or the development of adverse reactions. However, preliminary studies with a D1 agonist, ABT-431, are now in progress.