PACAP38 and PAC1 receptor blockade: a new target for headache?
Abstract Pituitary adenylate cyclase activating polypeptide-38 (PACAP38) is a widely distributed neuropeptide involved in neuroprotection, neurodevelopment, nociception and inflammation. Moreover, PACAP38 is a potent inducer of migraine-like attacks, but the mechanism behind this has not been fully elucidated. Migraine is a neurovascular disorder, recognized as the second most disabling disease. Nevertheless, the antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor are the only prophylactic treatment developed specifically for migraine. These antibodies have displayed positive results in clinical trials, but are not effective for all patients; therefore, new pharmacol…
Endothelin: an endothelium-derived vasoactive peptide and its possible role in the pathogenesis of cerebral vasospasm
The contractile response to endothelin has been examined in cerebral arteries from rats subjected to a prior subarachnoid haemorrhage (SAH) and compared with saline injected controls. Endothelin elicited strong concentration-dependent contraction of rat basilar artery segments. The response was slow in onset and long lasting. The endothelin-induced contraction was much stronger in the SAH compared to control animals. Our findings suggest a role of the peptide in the pathophysiology of cerebral vasospasm.
Blocking CGRP in migraine patients â a review of pros and cons
Abstract Migraine is the most prevalent neurological disorder worldwide and it has immense socioeconomic impact. Currently, preventative treatment options for migraine include drugs developed for diseases other than migraine such as hypertension, depression and epilepsy. During the last decade, however, blocking calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for prevention of migraine attacks. CGRP has been shown to be released during migraine attacks and it may play a causative role in induction of migraine attacks. Here, we review the pros and cons of blocking CGRP in migraine patients. To date, two different classes of drugs blocking CGRP have been developed: …