Olcegepant, a non-peptide CGRP1 antagonist for migraine treatment.
Olcegepant is the first potent and selective non-peptide antagonist of the calcitonin gene-related peptide 1 (CGRP1) receptor, a key modulator in neurogenic inflammatory pain. Under development by Boehringer Ingelheim GmbH, olcegepant is an intravenously formulated treatment for acute attacks of migraine. In preclinical studies, olcegepant attenuated arterial dilation induced by CGRP or electrical stimulation. In a phase II clinical trial, olcegepant reduced the severity of headache in 60% of migraine sufferers and met secondary endpoints including headache-free rate and rate of sustained response. Only mild-to-moderate transient adverse events were observed, with no adverse cardiovascular symptoms reported. The compound appears to be an effective anti-migraine medication that is well tolerated and does not display the vasoconstrictive effect that precludes the use of triptans and dihydroergotamine in certain patients. For a successful marketing of olcegepant, larger clinical trials and the development of an effective oral formulation will be necessary.
Department of Neurology, 2RCP, University of Iowa, Iowa City, IA 52242, USA. ana-recober@uiowa.edu
Ana
A
Recober
Andrew F
AF
Russo
D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D002116:Calcitonin / Q000037:antagonists & inhibitors*; D015740:Calcitonin Gene-Related Peptide; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004151:Dipeptides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D008881:Migraine Disorders / Q000188:drug therapy*; D015394:Molecular Structure; D010330:Patents as Topic; D010879:Piperazines; D011498:Protein Precursors / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome
D000700:Analgesics; C000606589:CALCA protein, human; D004151:Dipeptides; D010879:Piperazines; D011498:Protein Precursors; D011799:Quinazolines; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant