Safety and efficacy of PNU-142633, a selective 5-HT1D agonist, in patients with acute migraine.
In this randomized, double-blind, placebo-controlled, parallel-group study, patients received a single 50-mg oral dose of a 5-HT(1D) 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 after dosing, even after stratifying by baseline headache intensity. At 1 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 relief; 2.9% and 8.8% of the PNU-142633 group and 0% and 5.7% of the placebo group were free of headache pain. Adverse events associated with PNU-142633 treatment included chest pain (two patients) and QTc prolongation (three patients). Results from this study suggest that anti-migraine efficacy is not mediated solely through the 5-HT(1D) receptor subtype, although this receptor may contribute, at least in part, to the adverse cardiovascular effects observed with 5-HT agonist medications.
Gomez-Mancilla
B
B
Pharmacia & Upjohn Company, Kalamazoo, MI 491001-0199, USA. baltazar.gomez-mancilla@am.pnu.com
Cutler
N R
NR
Leibowitz
M T
MT
Spierings
E L
EL
Klapper
J A
JA
Diamond
S
S
Goldstein
J
J
Smith
T
T
Couch
J R
JR
Fleishaker
J
J
Azie
N
N
Blunt
D E
DE
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002839:Chromans / Q000009:adverse effects* / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000009:adverse effects* / Q000627:therapeutic use*
D002839:Chromans; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C401885:PNU 142633F