Dopamine receptor interactions: some implications for the treatment of Parkinson's disease

Since the discovery that L-DOPA could alleviate the symptoms of Parkinson's disease, it has been assumed that the striatum is the site of action of the dopamine formed from L-DOPA. However, for the past 15 years, evidence has accumulated to suggest that dopamine is also released by the dendrites of dopamine neurons in the substantia nigra and [D.sub.1] dopamine receptors in this region of the brain appear to play in important role in the actions of L-DOPA. Activation of [D.sub.1] receptors in the substantia nigra may, in part, explain some of the synergistic effects of [D.sub.1] and [D.sub.2] agonists in animal models for Parkinson's disease. These effects are discussed in light of recent studies suggesting that dopamine, acting on [D.sub.1] and [D.sub.2] dopamine receptor subtypes, activates distinct efferent pathways from the striatum. Clinical studies suggest that these findings may have important implications for the treatment of Parkinson's disease.
L-DOPA has longbeen known to relieve the symptoms of Parkinson's disease and was believed to have the striatum as the its site of action. However, evidence suggests that L-DOPA's conversion to dopamine and its activation of dopamine receptors also occur in other brain areas, particularly in the substantia nigra. Studies suggest that the activity of D1 receptors in the substantia nigra are related to the synergistic effects of D1 and D2 receptor agonists. Mechanisms underlying the role of dopaminergic drugs, specifically D1 and D2 agonists, on the movement of 6-OHDA-lesioned rats are believed to have numerous implicationsfor the treatment of Parkinson's disease.