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The Monoamine Oxidase Type B Inhibitor Rasagiline in the Treatment of Parkinson Disease: Is Tyramine a Challenge?
Author(s) -
Chen Jack J.,
Wilkinson Jayne R.
Publication year - 2012
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 - 10.1177/0091270011406279
Subject(s) - rasagiline , tyramine , monoamine oxidase , monoamine oxidase b , pharmacology , levodopa , parkinson's disease , clorgyline , medicine , selegiline , chemistry , monoamine oxidase a , disease , enzyme , biochemistry
Rasagiline is an irreversible monoamine oxidase type B (MAO‐B) inhibitor indicated for the treatment of the signs and symptoms of idiopathic Parkinson disease as initial monotherapy and as adjunct therapy to levodopa. Pharmacologic inhibition of monoamine oxidase type A (MAO‐A), but not MAO‐B, poses a risk of the “cheese effect,” a hypertensive response to excess dietary tyramine, a biogenic sympathomimetic amine. Tyramine challenge studies, conducted to characterize rasagiline selectivity for the MAO‐B enzyme and tyramine sensitivity, demonstrate that rasagiline, when used at the recommended dose, is selective for MAO‐B and is not associated with heightened tyramine sensitivity. This conclusion is also supported by safety results from large clinical trials of rasagiline in Parkinson disease involving 2066 rasagiline‐treated patients who did not require dietary tyramine restriction per protocol. In late 2009, US labeling for rasagiline was modified to state that dietary tyramine restrictions are not ordinarily required when rasagiline is administered at recommended doses. In addition, because rasagiline has been demonstrated to be selective for MAO‐B at the approved dose of up to 1 mg/d, contraindications regarding concomitant use with sympathomimetic amines, use of sympathomimetic vasopressors in conjunction with general or local anesthesia, and use in patients with pheochromocytoma also were removed.