Pharmacology & therapeutics
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Migraine is a highly prevalent neurovascular disorder that can be provoked by infusion of calcitonin gene-related peptide (CGRP). CGRP, a neuropeptide released from activated trigeminal sensory nerves, dilates intracranial and extracranial blood vessels and centrally modulates vascular nociception. On this basis, it has been proposed that: (i) CGRP may play an important role in the pathophysiology of migraine; and (ii) blockade of CGRP receptors may abort migraine. ⋯ However, recent data reported elevated liver transaminases when telcagepant was dosed twice daily for three months for the prevention of migraine rather than acutely. The potential for a specific acute antimigraine drug, without producing vasoconstriction or vascular side effects and with an efficacy comparable to triptans, is enormous. The present review will discuss the role of CGRP in the pathophysiology of migraine and the various treatment modalities that are currently available to target this neuropeptide.
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Review
Modulation of sensory nerve function and the cough reflex: understanding disease pathogenesis.
To cough is a protective defence mechanism that is vital to remove foreign material and secretions from the airways and which in the normal state serves its function appropriately. Modulation of the cough reflex pathway in disease can lead to inappropriate chronic coughing and an augmented cough response. Chronic cough is a symptom that can present in conjunction with a number of diseases including chronic obstructive pulmonary disease (COPD) and asthma, although often the cause of chronic cough may be unknown. ⋯ Therefore, in the hope of identifying novel antitussives, much research has focused on understanding the neural mechanisms of cough provocation. Experimentally this has been undertaken using chemical or mechanical tussive stimuli in conjunction with animal models of cough and clinical cough assessments. This review will discuss the neural mechanisms involved in the cough, changes that occur under pathophysiological conditions and and how current research may lead to novel therapeutic opportunities for the treatment of cough.