Merck is testing the a new drug for migraine that could be the first new way to treat the debilitating headaches in 18 years. The story of how that drug was discovered was told for the first time last Sunday at the American Chemical Society meeting in Chicago.
Until now, every new drug for migraines has worked on the same principle. All of the old drugs, including the leading class of chemicals called triptans, are vasoconstrictors, meaning they constrict blood vessels in the head, which reduces blood flow and prevents the release of chemicals that cause inflammation.
Daniel Paone and his team at Merck have discovered a small molecule calledMK-0974 that binds to and stops a migraine-related protein -- the calcitonin gene-related peptide receptor -- from working. Like most other drugs, it is an enzyme inhibitor.
This is where it gets weird. To prove that the drug is not a vasoconstrictor, they developed a noninvasive but unusual test. They dabbed a bit of the spicy chemical capsaicin onto a rhesus monkey's skin and then measured the blood flow in small capillaries with a Doppler laser. The capsaicin caused the capillaries to constrict. They compared that to the response of the blood vessels to their drug candidate. As expected, they found that it did not cause any vasoconstriction.
