Acute Treatments: Some Blind Alleys

SUMMARY

The introduction of sumatriptan, a selective 5-HT1B/1D agonist, for the treatment of migraine sparked a new era of drug research in this field. Many novel targets have since been developed, and tested in the clinic. The promise of these approaches is to deliver an anti-migraine compound with the optimal efficacy and safety profile. In this chapter, blind alleys in anti-migraine development are discussed. The falling soldiers have included

the NK-1 antagonists, some second-generation 5-HT1B/1D agonists, CP-122,288, 4991W93, the neurosteroid ganaxolone, selective 5-HT1F (LY334370) and 5-HT1D agonists (PNU-142,633), and the endothelin-1 antagonist bosentan. Some of these promising targets failed to demonstrate clinical efficacy, while others were stopped for preclinical toxicity.

Keywords: :

• Acute therapy
• Animal models
• Migraine
• Pathogenesis
• Randomized controlled trials
• Receptor target
• Transitional research