Transcription of CGRP antagonists: hope for a new era in acute …
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CGRP antagonists: hope for a new era in acute …
AbstractCalcitonin gene-related peptide (CGRP) has a wide-spread distribution throughout the trigeminovascular system and other brain areas involved in migraine patho-genesis. Serum levels of CGRP are elevated during themigraine attack and return to normal with alleviation ofpain. Intravenous injection of CGRP in migraineursresults in delayed headache similar to migraine . SinceCGRP receptor antagonists lack direct vasoconstrictoractivity, this therapeutic approach may offer advantagesover the current mainstay of specific acute migraine treatment with 5-HT1B/1D receptor agonists (triptans),contra-indicated in patients with underlying cardio -vascular disease. Intravenous BIBN4096BS (olcegepant)and oral MK-0974 (telcagepant), two CGRP-receptor antagonists, were safe and effective in the treatment ofmigraine attacks in Phase I and II trials. In a Phase IIIclinical trial, the efficacy of telcagepant 300 mg was comparable to that of zolmitriptan 5 mg.
CGRP ANTAGONISTS IN MIGRAINE 253 this complex mainly leads to activation of adenylate cyclase, thereby increasing intracellular cAMP …
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