Piribedil

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Piribedil is a nonergoline selective D2/D3 agonist with alpha-1 antagonist activity. Oral doses of this medication range between 80 and 250 mg/d. Once blood levels are stabilized with a piribedil dose of at least 150 mg/d, it has a mean half-life of approximately 21 hours.

Simon et al. (54) assessed the efficacy of a single intravenous infusion of piribedil in 10 subjects with PD who received escalating doses of piribedil (2, 4, 8, and 16 mg) or placebo. These subjects continued their PD medications, including dopamine agonists, levodopa, catechol-O-methyl-transferase (COMT) inhibitors, anticholinergic drugs, and amantadine, but they were withheld 12 hours before and up to three hours after the infusion. In addition, patients were pretreated with the antiemetic, domperidone prior to the infusion. This study showed improvement in wearing off in 7 out of 10 subjects. Motor status, including akinesia, improved at 15 minutes with a maximum benefit at one hour and effects continuing up to three hours, even with the lowest dose of 2 mg. Mild-to-moderate side effects were seen at the 8-mg dose and above and included flushing, nausea, vomiting, abdominal pain, and somnolence (54).

Several studies demonstrated the efficacy of piribedil as monotherapy and as an adjunct to levodopa. Castro-Caldas et al. (55) performed a 12-month, randomized, double-blind study evaluating the benefit of piribedil (150 mg/d) on motor function compared to bromocriptine (25 mg/d) as adjunct therapy with levodopa in 425 PD subjects. There were no significant differences between piribedil (58.4% response) and bromocriptine (55.3%) in UPDRS motor scores, response rate, or cognitive performance. Although subjects randomized to piribedil required less levodopa increase than those on bromocriptine (7.6 ± 121.9 mg vs. 16.7 ± 91.3 mg), this was not significant.

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