New Agents for Acute Treatment of Migraine: CGRP Receptor Antagonists, iNOS Inhibitors
Headache (JR Couch, Section Editor)
First Online: 17 November 2011 DOI:
10.1007/s11940-011-0155-4 Cite this article as: Hoffmann, J. & Goadsby, P.J. Curr Treat Options Neurol (2012) 14: 50. doi:10.1007/s11940-011-0155-4 Opinion statement
The treatment of migraine was advanced dramatically with the introduction of triptans in the early 1990s. Despite the substantial improvement in the quality of life that triptans have brought to many migraineurs, a substantial cohort of patients remain highly disabled by attacks and need new therapeutic approaches, which ideally should be quick-acting, have no vasoconstrictor activity, and have a longer duration of action and be better tolerated than current therapies. The calcitonin gene-related peptide (CGRP) receptor antagonists (gepants)—olcegepant (BIBN 4096 BS), telcagepant (MK-0974), MK3207, and BI 44370 TA—are effective in treating acute migraine. They have no vasoconstrictive properties, fewer adverse effects, and may act longer than triptans. Their development has been complicated by liver toxicity issues when used as preventives. Results from studies with BI 44370 TA do not support broad concern about a class effect, and further studies are ongoing in this respect. Many experimental studies and clinical trials suggest that nitric oxide may have a role in the pathophysiology of migraine. Therefore, the inhibition of nitric oxide synthase (NOS) for the acute or prophylactic treatment of migraine offered a feasible approach; as inducible NOS (iNOS) is involved in several pain states, such as inflammatory pain, it appeared to be an attractive target. However, despite high selectivity and potency, the iNOS inhibitor GW274150 was not effective for acute treatment or prophylaxis of migraine, suggesting that iNOS is very unlikely to be a promising target.
Keywords Migraine Treatment Drug therapy Pathophysiology CGRP receptor antagonists Calcitonin gene-related peptide Gepants Olcegepant BI 44370 TA Telcagepant Prophylaxis iNOS inhibitors GW274150 References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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