Clinical pharmacology tyramine challenge study to determine the selectivity of the monoamine oxidase type B (MAO-B) inhibitor rasagiline.
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.
Goren
Tamar
T
Teva Pharmaceutical Industries Ltd, PO Box 8077 Kiryat Nordau, Netanya, Israel. tamar.goren@teva.co.il
Adar
Liat
L
Sasson
Nissim
N
Weiss
Yoni M
YM
D000328:Adult; D000368:Aged; D000465:Algorithms; D000075202:Contraindications; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004348:Drug Labeling; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007189:Indans / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy; D012642:Selegiline / Q000494:pharmacology; D014439:Tyramine / Q000009:adverse effects; D014481:United States
D007189:Indans; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D012642:Selegiline; D008734:Methoxyhydroxyphenylglycol; D008995:Monoamine Oxidase; C010117:3,4-dihydroxyphenylglycol; D014439:Tyramine