Migraine and beyond: cardiovascular therapeutic potential for CGRP modulators

CGRP is a potent vasodilator that has been shown to have a physiological an d/or pathological role in neurogenic inflammation, headaches including migr aine, thermal injury, circulatory shock, pregnancy and menopause, hypertens ion and heart failure and is known to be cardioprotective. CGRP is also a p ositive inotrope and increases heart rate. Clinical trials have shown benef icial effects of the vasodilatory action of CGRP in hypertension, angina, h eart failure, Raynaud's disease and venous stasis ulcers. However, the clin ical potential of CGRP is limited as it has to be given by infusion and is quickly broken down. Oral long acting CGRP-mimetics may have potential in d isorders in which CGRP has been shown to be beneficial. CGRP-mimetics inclu de capsaicin/vanilloid receptor agonists and gene transfer of an adenoviral vector that encodes prepro-CGRP. CGRP inhibitors have therapeutic potentia l in conditions in which excessive CGRP-mediated vasodilatation is present; neurogenic inflammation, migraine and other headaches, thermal injury, cir culatory shock and flushing in menopause. CGRP inhibitors include capsaicin , antagonists at capsaicin/vanilloid receptors, civamide, CGRP receptor ant agonists and 5-HT1D-receptor agonists. Drugs that are 5-HT1D-receptor agoni sts, the 'triptans' are already commonly used in migraine and the first sma ll molecule CGRP antagonist, BIBN4096BS, is under clinical investigation fo r the treatment of migraine.