Migraine and the pharmaceutical industry

A short history of medicines development in migraine

For most of human history there have been no remedies for migraine other than herbal brews and folk practices. In 1200 BC the Egyptians advocated binding a clay crocodile with magic herbs in its mouth to the head of the patient. In the tenth century AD physicians in Arabia applied a hot iron or garlic to an incision in the temple. By the mid-1600s AD Dr Thomas Willis was using enemas, blood letting, leeches, and natural products including vinegar, nutmeg, rosemary, amber, crab’s eyes, coral, millipedes and woodlice. In fairness, he also used mild analgesic and hypnotic extracts for those in need. Even as late as the 1870s, the best recommendation was a cold bandage round the head, quiet and, if possible, sleep.

The move towards the use of medicines began in 1868 with a paper published in the British Medical Journal on the use of ergot of rye in the treatment of neuralgia, including one-sided headache. Ergot is a parasitic fungus infection of certain grass species in which the seed heads are replaced by black spore-bearing structures. For some time it had been known that ergot extract contained biologically active chemicals and after 1868 it began to be used in migraine, either alone or combined with bromide or nitroglycerine, depending on whether there was facial flushing or pallor. Even so, it took until 1925 to identify the active chemical ergotamine was identified and 1928 before it was introduced into clinical practice. Experiments by the Nobel Prize winner, Sir Henry Dale, showed that the compound could inhibit pain and by the 1940s ergotamine tartrate had become the preferred treatment for acute migraine.

Ergotamine is still available in several different forms to suit different patient needs, but is not free of side effects. Because of this, efforts were made to find better-tolerated forms of it. One, dihydroergotamine, has far fewer unwanted effects on arteries outside the brain and hence fewer side effects. Another substance from the ergot family, methysergide, was developed in the 1960s.

It acts somewhat differently to ergotamine and can be used to prevent attacks. Other preventive agents have also been introduced, including cyproheptadine, pizotifen and some medicines developed initially to treat high blood pressure. This last group includes clonidine and several beta-blockers, the first of which to be introduced for migraine was propranolol.

A most important advance took place in the early 1980s as a result of increased understanding of migraine mechanisms. This resulted in the identification of a more selective compound beneficial in the treatment of acute attacks. It was subsequently named sumatriptan and went on to become the first of a new class of anti-migraine compounds called the triptans. These now make a major contribution to the management of migraine.