Acute treatments: some blind alleys.
The introduction of sumatriptan, a selective 5-HT(1B/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 failing soldiers have included the NK-1 antagonists, some second-generation 5-HT(1B/1D) agonists, CP-122,288, 4991W93, the neurosteroid ganaxolone, selective 5-HT(1F) (LY334370) and 5-HT(1D) 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.
Ramadan
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Lilly Research Laboratories, Eli Lilly & Co. and Indiana University School of Medicine, Indianapolis, Indiana 46285, USA. ramadan@lilly.com
D004353:Drug Evaluation, Preclinical; D019332:Endothelin-1 / Q000037:antagonists & inhibitors*; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy*; D064729:Neurokinin-1 Receptor Antagonists; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*
D019332:Endothelin-1; D064729:Neurokinin-1 Receptor Antagonists; D017366:Serotonin Receptor Agonists