Transtelephonic Home Blood Pressure to Assess the Monoamine Oxidase-B Inhibitor Rasagiline in Parkinson Disease

Abstract

Abstract-Monoamine oxidase inhibitors are associated with dietary tyramine interactions that can induce hypertensive crises. Rasagiline mesylate is a novel irreversible selective monoamine oxidase type B inhibitor for Parkinson disease that may have a low risk of interaction with dietary tyramine because of its selectivity. To study interactions of rasagiline with diets unrestricted in tyramine-containing foods, we incorporated transtelephonic, self-monitoring of the blood pressure (BP) into a randomized, placebo-controlled trial of rasagiline 0.5 and 1.0 mg daily in 414 levodopa-treated Parkinson patients with motor fluctuations. The proportion of patients with a systolic BP increase of Ͼ30 mm Hg was the primary BP end point. In 13 968 self-measured readings at baseline, the proportion of systolic BP values that increased by Ͼ30 mm Hg after a meal ranged from 9.5% to 12.9% in the 3 treatment groups. In 25 733 BPs obtained postrandomization, the proportion of values with a Ͼ30-mm Hg systolic postprandial increase was 15% in the placebo group, 15% in the rasagiline 0.5-mg group, and 11% in the rasagiline 1-mg group after 3 weeks of double-blind therapy and 13%, 14%, and 12%, respectively, after 26 weeks of treatment (P value was not significant for all of the comparisons among treatment groups). A postprandial increase in systolic BP to Ͼ180 mm Hg at any time after randomization was seen in 3.3%, 2.6%, and 2.9% of the placebo, 0.5-mg, and 1.0-mg rasagiline groups, respectively. These data demonstrate that rasagiline did not induce postprandial hypertension in patients with Parkinson disease who were on an unrestricted diet. is commonly complicated by motor fluctuations and dyskinesias, which cause substantial morbidity for patients with this disorder. 1 Inhibitors of monoamine oxidase (MAO) type B (MAO-B), the main enzyme that metabolizes dopamine in the brain, may potentiate the beneficial motor effects of the dopaminergic agents and reduce the severity of motor complications. 2,3 Rasagiline (N-propargyl-1-(R)-aminodan) mesylate is a new irreversible MAO-B inhibitor with high selectivity for the B isoform of the enzyme shown to improve function in patients with Parkinson disease. 4,5 Tyramine is an amino acid present in high concentrations in certain food types (aged cheeses, fermented meats, and sauerkraut) that can generate pressor responses unless it is metabolized by MAO in the gastrointestinal tract. 6 The usefulness of nonselective MAO inhibitors for depression has been limited by the need to restrict dietary tyramine intake to avoid potentially severe hypertensive reactions. Selective MAO-B inhibitors, such as rasagiline, are relatively free of this limitation, because 90% of MAO activity in the intestine involves the MAO type A isoform. 7 However, it is not clear whether the selectivity is adequate at higher doses or in tyramine-sensitive individuals.To evaluate the safety of rasagiline in patients with an unrestricted diet, we performed a large novel study of selfmonitored transtelephonic blood pressure...

Rasagiline: A Review of Its Use in the Treatment of Idiopathic Parkinson’s Disease

“…aged cheese), are not expected with the selective MAO-B inhibitor rasagiline. Tyramine challenge studies [26][27][28] and home BP monitoring in patients on unrestricted diets [29] have shown that, at the recommended therapeutic dosage of 0.5-1 mg/day, rasagiline is not associated with significant tyramine pressor responses, indicating that restrictions on dietary tyramine are unnecessary. However, there have been postmarketing reports of pressor responses to high dietary tyramine ingestion in patients taking rasagiline; therefore, it is recommended in the prescribing information that patients avoid tyraminerich foods [5].…”

Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury

“…For decades, this side-effect was the major drawback for the use of MAO inhibitors in clinic. However, non-reversible MAO-B inhibitors and RIMAs are devoid of these undesirable effects and can be used by patients on unrestricted diet [136]. Thus, considering the availability of these amenable inhibitors and the encouraging results obtained with MAO inhibitors in experimental CHF and I/R injury, MAO inhibition might represent a potential new class of compounds to employ for treatment of ischemic and non ischemic cardiac disorders.…”

Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide

“…For drugs with off-target effects associated with increases in BP, out-of-office monitoring has been shown to be effective in ascertaining the extent and duration of pharmacodynamic effects during both phases 2 and 3 clinical development [6,7]. Hence, we conducted a large, multicenter, randomized, double-blind, placebo-controlled, and parallel-group trial of three different doses of bremelanotide administered subcutaneously on an at-home, as-needed basis for up to 12 weeks by premenopausal women with sexual dysfunction syndromes.…”