In this randomized, double-blind, placebo-controlled, parallel-group study,
patients received a single 50-mg oral dose of a 5-HT1D agonist, PNU-142633
(n = 34), or matching placebo (n = 35) during an acute migraine attack. No
statistically significant treatment effects were observed at 1 and 2 h aft
er dosing, even after stratifying by baseline headache intensity. At I and
2 h post-dose, 8.8% and 29.4% of the PNU-142633 group, respectively, and 8.
6% and 40.0% of the placebo group, respectively, experienced headache relie
f; 2.9% and 8.8% of the PNU-142633 group and 0% and 5.7% of the placebo gro
up were free of headache pain. Adverse events associated with PNU-142633 tr
eatment included chest pain (two patients) and QTc prolongation (three pati
ents). Results from this study suggest that anti-migraine efficacy is not m
ediated solely through the 5-HT1D receptor subtype, although this receptor
may contribute, at least in part, to the adverse cardiovascular effects obs
erved with 5-HT agonist medications.