It’s hard to believe that it took decades of research and false starts before we had a breakthrough in migraine treatment. But then, in 1992, sumatriptan was approved, offering new hope for those suffering from these debilitating headaches.
The journey to get there was long and winding, filled with twists and turns. It all started with the discovery of serotonin in the late 1940s. This important neurotransmitter had been identified as a potential player in migraine, but it took years of research to understand its role.
Initially, scientists thought that blood vessels in the brain were the culprit behind migraines. The theory was that these vessels would stretch and widen, causing pain. But this didn’t quite add up. People don’t get headaches from exercising or taking a hot bath, after all! So researchers expanded on the idea, proposing that there might be a chemical that caused tissue around blood vessels to swell, lowering the pain threshold.
Serotonin seemed like a prime suspect. And indeed, studies showed that injecting serotonin into people could trigger migraine symptoms. This led scientists to search for a medication that would block serotonin receptors – also known as 5-HT receptors.
Enter LSD, a drug notorious for its hallucinogenic effects. While it was great at blocking 5-HT receptors, it wasn’t exactly the kind of treatment you’d want to recommend to your patients! So researchers modified the chemical structure of LSD to create methysergide, which blocked 5-HT receptors without the hallucinations.
In 1962, methysergide was approved for migraine prevention. While it worked well, it came with some serious side effects – including fibrosis, or scarring, that could damage the heart and arteries. Today, it’s no longer recommended for migraine prevention and is not available in the United States.
Despite the setbacks, research on methysergide led to an important discovery: there are several different 5-HT receptor subtypes, and each one responds differently to medications. This finding would later play a key role in the development of sumatriptan – a medication that has become a go-to treatment for many people.
But here’s the thing: early researchers may have misunderstood the role of serotonin in migraine. They thought they needed to reduce serotonin levels, but it turns out that serotonin levels actually decrease at the start of a migraine attack! When this happens, blood vessels in the brain stretch out. So, what was needed was a drug that would mimic serotonin’s effects on these blood vessels.
And that’s exactly what sumatriptan does – by binding to 5-HT1B and 5-HT1D receptors in the brain, it helps reduce swelling in blood vessels and relieve migraine symptoms. Today, we believe that migraines are neurovascular diseases, meaning they involve both nerves and blood vessels. And while we’re still not entirely sure how triptans work their magic, one thing is clear: they’ve become a common first-line treatment for stopping moderate-to-severe migraine attacks.
So the next time you reach for your trusty sumatriptan tablet or nasal spray, remember the long journey that led to its development – and the scientists who refused to give up in the face of setbacks.
