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.