Pressor response to intravenous tyramine in healthy subjects after safinamide, a novel neuroprotectant with selective, reversible monoamine oxidase B inhibition.
Safinamide is a novel neuroprotectant combining sodium and calcium channel blocking properties with selective, reversible monoamine oxidase type B (MAO B) inhibition. Phase 1 studies have demonstrated that in healthy volunteers, the ED50 (a dose that inhibits enzyme activity by 50% in 50% of treated subjects) for MAO B inhibition is 87.5 microg/kg/day orally, and that no MAO A inhibition occurs after 10-mg/kg oral dosing. To assess the risk of inducing the "cheese effect," the effect of safinamide and placebo on the pressor response to tyramine was investigated in a group of healthy male volunteers. The study was an open, single-dose placebo-controlled trial with the 2 treatments in sequence. An increase of 30 mm Hg systolic blood pressure was obtained by intravenous tyramine administered by 0.5-mg incremental boluses injected at 15-minute intervals. The amount of tyramine necessary to achieve such a blood pressure increase was the same after the safinamide 2-mg/kg oral load compared with placebo. These results suggest that dietary restrictions for food with high tyramine content should not be required under safinamide treatment.
Cattaneo
Carlo
C
Newron Pharmaceuticals S.p.A, Via Ludovico Ariosto 21, 20091 Gerenzano, Italy.
Caccia
Carla
C
Marzo
Antonio
A
Maj
Roberto
R
Fariello
Ruggero G
RG
D000328:Adult; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000704:Analysis of Variance; D001596:Benzylamines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004334:Drug Administration Schedule; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008995:Monoamine Oxidase / Q000097:blood*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000201:enzymology; D014439:Tyramine / Q000008:administration & dosage / Q000494:pharmacology*
D001596:Benzylamines; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; C092797:safinamide; D008995:Monoamine Oxidase; D000409:Alanine; D014439:Tyramine