The dopamine agonists used in the treatment of PD include: apomorphine, bromocrip-tine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, and rotigotine. All of these agents activate D2 receptors, whereas pergolide has been shown to be a mild D1 agonist, and pramipexole may have higher affinity for D3 receptors (Table 1). Five subtypes of dopamine agonist receptors have been identified and may be classified into striatal (D1 and D2) receptors or cortical (D3, D4, and D5) receptors. The D3-5 receptors are present in the mesolimbic and mesocortical dopaminergic pathways. The D1-receptor (D1,5) family is associated with activation of adenylate cyclase and dopamine, and dopamine agonists activate the D2-receptor family (D2-4) (6). Postmortem examination of brains of patients with PD revealed upregulation of stri-atal D2 and downregulation of the D1 receptors. It is postulated that these changes lead to alteration of the indirect D2-mediated pathway and disinhibition of the sub-thalamic nucleus (STN). Studies comparing apomorphine, a rapid acting dopamine agonist, to deep brain stimulation found comparable changes in Unified Parkinson's Disease Rating Scale (UPDRS) and intracortical inhibition with STN stimulation, globus pallidus stimulation, and apomorphine infusion, suggesting a connection between the nigral dopaminergic pathway and the thalamocortical motor pathway (7).
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