Clinical pharmacology tyramine challenge study to determine the selectivity of
the monoamine oxidase type B (MAO-B) inhibitor rasagiline.
Author(s): Goren T, Adar L, Sasson N, Weiss YM.
Affiliation(s): Teva Pharmaceutical Industries Ltd, PO Box 8077 Kiryat Nordau, Netanya, Israel.
tamar.goren@teva.co.il
Publication date & source: 2010, J Clin Pharmacol. , 50(12):1420-8
Rasagiline is a selective, monoamine oxidase (MAO)-B inhibitor indicated for
treatment of Parkinson's disease. This double-blind, placebo-controlled study
determined the tyramine sensitivity factor (TSF) and degree of MAO-A inhibition
(ie, reduction in plasma dihydroxyphenylglycol) in healthy volunteers who
received phenelzine (15 mg, 3 times daily; positive control), selegiline (5 mg,
twice daily), or rasagiline (1-6 mg, once daily) for 14 days or rasagiline 2 mg/d
for 30 days. The selegiline/rasagiline groups were randomized to placebo or
active drug. TSF was highest with phenelzine (17.3) and lowest with placebo
(1.5). TSF with selegiline was 2.5. TSFs for rasagiline were as follows: 2.0 for
1 mg/d; 3.3 and 2.4 for 2 mg/d administered for 14 and 30 days, respectively; 4.5
for 4 mg/d; and 5.1 for 6 mg/d. Plasma dihydroxyphenylglycol concentrations
suggested that rasagiline 1 mg/d had no effect, whereas rasagiline 2 mg/d had
only minimal effect. In contrast, rasagiline 4 and 6 mg/d reduced
dihydroxyphenylglycol to a degree approaching that achieved by the positive
control phenelzine. Results demonstrate that rasagiline selectively inhibits
MAO-B and is not associated with increased tyramine sensitivity at the indicated
dose (1 mg/d). These data allowed removal of dietary tyramine restriction from
rasagiline US labeling.
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