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Clinical Pharmacology Tyramine Challenge Study to Determine the Selectivity of the Monoamine Oxidase Type B (MAO‐B) Inhibitor Rasagiline
Author(s) -
Goren Tamar,
Adar Liat,
Sasson Nissim,
Weiss Yoni M.
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010369674
Subject(s) - rasagiline , selegiline , phenelzine , pharmacology , monoamine oxidase , tyramine , placebo , monoamine oxidase b , chemistry , medicine , parkinson's disease , enzyme , biochemistry , alternative medicine , disease , pathology
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.