Pressor Response to Oral Tyramine and Monoamine Oxidase Inhibition During Treatment with Ralfinamide (NW-1029)

Abstract

Ralfinamide, an original Na(+) channel blocker developed for the treatment of chronic pain, inhibits monoamineoxidase-B with no apparent effect on monoamineoxidase-A. To evaluate the pressor response to oral tyramine under fasting conditions during treatment with ralfinamide in healthy normotensive subjects. Ten women and 10 men aged 52.9±5.5, sensitive to the oral tyramine pressor effect in the dose range 200-400mg, received ralfinamide 320mg daily during 7days of confinement. Starting on day 5, ascending doses of tyramine 50, 100 and 200mg were daily administered to subjects, who had responded to 200mg at screening, and 100, 200 and 400mg to the 400mg responders. Vital parameters were monitored. The systolic blood pressure peak (ΔSBP), the time to achieve the peak (Δt) and the area under the pressure curve (over baseline) were calculated. ΔSBP≥30mmHg were measured for one subject with tyramine 200mg and for 11 subjects with 400mg, whilst ΔSBP was <30mmHg for eight subjects at all the tested doses. ΔSBP, Δt and AUC after co-treatment with ralfinamide and tyramine were not significantly different from those measured after tyramine alone. Ralfinamide did not potentiate the pressor response to single oral doses of tyramine from 50 to 400mg. These preliminary results give an evidence for the specificity of ralfinamide for MAO-B in comparison with MAO-A, analogously to the observations previously done for safinamide. Dietary tyramine restrictions may not be necessary in neuropathic pain patients receiving ralfinamide as a therapy.