While
triptans, the 5-HT1B/1D agonists, are effective and generally well-tolerated in many patients up to one-third of
migraine patients either may not respond well to
triptans, may not tolerate their side effects, or may have
contraindications that preclude their use. Recurrence,
triptan-related side effects, and cardiovascular constriction effects are demerits for acute
migraine treatment.
CGRP receptor antagonists, the so-called
gepants, were clearely designed and expected to be better than
triptans. CGRP is located in sensory nerve endings around cranial blood vessels. CGRP is a strong dilator of cerebral arteries and
intravenous infusion of CGRP cause a
migraine attack.
Olcegepant is the first selective
CGRP receptor antagonist of proven efficacy in
migraine.
Olcegepant could only be administered intravenously and never taken beyond Phase II.
Telcagepant is orally available and several completed Phase III trials have revealed positive results. In several comparative studies of
telcagepant and
triptans, telcegepant did not appeared more effective than
zolmitriptan or
rizatriptan, although it had fewer
triptan-related adverse events and
drug-related adverse enents. A small number of patients taking
olcegepant showed marked elevation in liver
transaminase levels. It was decided to discontinue development of
olcegepant. New
CGRP receptor antagonists would be expected for acute
migraine treatment.