title: The effect of safinamide, a novel drug for Parkinson's disease, on pressor response to oral tyramine: a randomized, double-blind, clinical trial.
abstract: This randomized, double-blind, placebo-, comparator (selegiline 10 mg/day)-, and positive (phenelzine 30 mg/day)-controlled study investigated the pressor response to oral tyramine under fasting conditions after the administration of safinamide at therapeutic (100 mg/day) and supratherapeutic (350 mg/day) dosing regimens in healthy volunteers for the purpose of assessing the need for dietary restrictions. Pressor response was characterized by Tyr30, defined as the tyramine dose that triggers a sustained increase in systolic blood pressure (SBP) of ≥30 mm Hg as compared with baseline SBP. The primary end point was the tyramine sensitivity factor (TSF), defined as the ratio of Tyr30 at screening to Tyr30 under treatment. Safinamide induced a mild increase in TSF; however, the effect at each of the doses was numerically lower than those of the comparators (geometric mean TSFs: placebo, 1.52; safinamide 100 mg, 2.15; safinamide 350 mg, 2.74; selegiline, 3.12; phenelzine, 9.98). This study confirms that safinamide is a highly selective monoamine oxidase-B inhibitor, even at supratherapeutic doses, and suggests that it can be administered without tyramine-related dietary restrictions.
authors.affiliation: Global Exploratory Medicine, Merck Serono S.A., Geneva, Switzerland. anne.marquet@merckgroup.com
authors.forename: A
authors.initials: A
authors.lastname: Marquet
authors.forename: K
authors.initials: K
authors.lastname: Kupas
authors.forename: A
authors.initials: A
authors.lastname: Johne
authors.forename: B
authors.initials: B
authors.lastname: Astruc
authors.forename: A
authors.initials: A
authors.lastname: Patat
authors.forename: S
authors.initials: S
authors.lastname: Krösser
authors.forename: A
authors.initials: A
authors.lastname: Kovar
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001596:Benzylamines / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014439:Tyramine / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D001596:Benzylamines; C092797:safinamide; D000409:Alanine; D014439:Tyramine