title: The monoamine oxidase type B inhibitor rasagiline in the treatment of Parkinson disease: is tyramine a challenge?
abstract: 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.
authors.affiliation: Department of Neurology, School of Medicine and Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Loma Linda University, Loma Linda, CA, USA. jjchen@llu.edu
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Chen
authors.forename: Jayne R
authors.initials: JR
authors.lastname: Wilkinson
mesh_terms: D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004044:Dietary Proteins / Q000009:adverse effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018565:Food-Drug Interactions; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000201:enzymology; D061214:Patient Safety; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D014439:Tyramine / Q000009:adverse effects / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D004044:Dietary Proteins; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D008995:Monoamine Oxidase; D014439:Tyramine