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New Agents for Acute Treatment of Migraine: CGRP Receptor Antagonists, iNOS Inhibitors.

Department of Neurology, University of California, San Francisco, 1701 Divisadero Street, Suite 480, San Francisco, CA, 94115, USA.
Current Treatment Options in Neurology (Impact Factor: 2.18). 11/2011; 14(1):50-9. DOI: 10.1007/s11940-011-0155-4
Source: PubMed

ABSTRACT 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.

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    • "The neuropeptide calcitonin gene-related peptide (CGRP) is hypothesized to play an important role in migraine pathology (Durham, 2008; Ho et al., 2010). Serum levels of CGRP are increased during migraine attack (Goadsby et al., 1990) (however, see Tvedskov et al., 2005); migraine patients infused with CGRP develop a delayed headache, fulfilling the criteria of a migraine (Lassen et al., 2002); and infusion of CGRP receptor antagonists have been shown to effectively treat migraine pain (Durham and Vause, 2010; Fischer, 2010; Hoffmann and Goadsby, 2011). Importantly, treatment of migraine headache pain with sumatriptan has been shown to correlate with normalization of CGRP levels e an effect that paralleled migraine resolution (Edvinsson and Ho, 2010; Goadsby and Edvinsson, 1993; Sarchielli et al., 2006; Stepien et al., 2003). "
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