The Food and Drug Administration (FDA) approved apomorphine, a nonergoline dopamine agonist, as a subcutaneously injected treatment for severe off episodes in 2004. It was first used in the 1930s as an emetic and was found to have benefit for PD over 50 years ago. Although the mechanism of action is unclear, it is thought that apomorphine ameliorates symptoms of PD by stimulating D2 receptors within the caudate nucleus and putamen. It has a high affinity for D4 receptors; moderate affinity for D2, D3, and D5; moderate affinity for adrenergic receptors; and low affinity for D1 and 5-hydroxytryptamine (5-HT) receptors (Table 1). In addition to the FDA-approved formulation administered subcutaneously, it has also been administered as an intravenous infusion, intranasal spray, sublingual tablet, and as a rectal suppository (8). Although intravenous administration of apomorphine results in consistent motor control, allowing for a reduction in oral medications, unanticipated intravascular thrombotic complications, secondary to apomorphine crystal accumulation, have led to termination of this route of administration (9). Subcutaneously administered apomorphine has a rapid onset of 7.3 to 14 minutes after administration and a short half-life of 45 to 90 minutes. The rate of uptake after apomorphine injection is influenced by factors such as location, temperature, depth of injection, and body fat. Plasma protein binding of apomorphine is approximately 30%, and its metabolism is unclear (Table 2) (10).

Apomorphine may be given subcutaneously every two hours. A test dose of 2 mg is administered to determine the initial dosing, and may be titrated to an effective dosage by 1 mg increments up to a maximum single exposure of 6 mg (11). There are limited data for dosing over five times per day, and at this dosing frequency, continuous subcutaneous infusion should be considered. Side effects of apomorphine include nausea, vomiting, QT-interval prolongation on EKG, and hypotension. Because of the powerful emetic action of apomorphine, treatment is initiated three

TABLE 2 Dopamine Agonists in Parkinson's Disease

Dopamine agonist



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