Reyvow: A New Kind of Migraine Treatment

Reyvow (lasmiditan) works differently from every other acute migraine medication on the market. It's the first and only FDA-approved medication in a drug class called ditans. Understanding how it works helps explain both its benefits and its limitations — including why it comes with an 8-hour driving restriction.

Note: Eli Lilly is permanently discontinuing Reyvow, with U.S. distribution ending May 31, 2026. For details on the discontinuation, see our Reyvow discontinuation update.

The Basics: What Happens During a Migraine

To understand how Reyvow works, it helps to understand what's happening in your brain during a migraine.

Migraine isn't just a bad headache. It's a complex neurological event involving the trigeminal nerve system — a major nerve pathway that carries pain signals from your face and head to your brain.

During a migraine:

1. The trigeminal nerve gets activated. Something triggers the nerve fibers surrounding blood vessels in your brain.
2. Neuropeptides are released. The activated nerve fibers release chemicals called neuropeptides, including CGRP (calcitonin gene-related peptide). These chemicals cause inflammation and pain signaling.
3. Pain signals reach the brain. The brain processes these signals as intense, throbbing head pain, often accompanied by nausea, light sensitivity, and sound sensitivity.

How Reyvow Stops the Migraine

Reyvow works by targeting a specific receptor in the brain called the serotonin 5-HT1F receptor.

Here's what that means in plain English:

Step 1: Reyvow Activates 5-HT1F Receptors

When you take Reyvow, the medication travels to your brain and selectively binds to (activates) serotonin 5-HT1F receptors. These receptors are found on nerve cells in the trigeminal pathway — the same pathway that's causing your migraine pain.

Step 2: Nerve Firing Slows Down

By activating these receptors, Reyvow tells the overactive trigeminal nerve cells to calm down. It inhibits neuronal firing, which means fewer pain signals are sent from the trigeminal system to your brain.

Step 3: Neuropeptide Release Is Reduced

Reyvow also reduces the release of inflammatory neuropeptides from the trigeminal nerve endings. Less inflammation means less pain.

The Result

Within about 1–2 hours, many patients experience significant reduction in headache pain, nausea, and sensitivity to light and sound.

How Reyvow Is Different From Triptans

For decades, triptans (like Sumatriptan, Rizatriptan, and Zolmitriptan) have been the go-to acute migraine treatment. Triptans work on a similar principle — they activate serotonin receptors to reduce migraine symptoms. But they target different receptors:

The most important difference is vasoconstriction. When triptans activate 5-HT1B receptors on blood vessels, those vessels narrow. For most people, this is fine. But for patients with coronary artery disease, a history of heart attack or stroke, peripheral vascular disease, or uncontrolled hypertension, vasoconstriction can be dangerous.

Reyvow's 5-HT1F receptor target is not found on blood vessels. This means Reyvow treats migraine pain through a purely neuronal mechanism — no blood vessel narrowing involved. This made Reyvow a valuable option for patients who couldn't safely use triptans.

How Reyvow Is Different From CGRP Medications

Newer migraine medications like Ubrelvy (ubrogepant), Nurtec ODT (rimegepant), and Zavzpret (zavegepant) work by a completely different mechanism. They block CGRP receptors, preventing the neuropeptide CGRP from triggering inflammation and pain.

Here's how they compare:

• Reyvow works upstream — it stops the trigeminal nerve from firing and releasing neuropeptides in the first place.
• CGRP antagonists work downstream — they block the effect of neuropeptides that have already been released.

Both approaches are effective. CGRP antagonists have the advantage of no driving restriction and no controlled substance classification. However, some patients respond better to one mechanism than the other. For a full comparison, see our alternatives to Reyvow guide.

Why Does Reyvow Cause Dizziness and Drowsiness?

The 5-HT1F receptors that Reyvow targets aren't only found in the trigeminal pain pathway. They're also present in other parts of the brain involved in alertness, coordination, and motor function.

When Reyvow activates these receptors throughout the brain, it can cause:

• Dizziness — from effects on the vestibular (balance) system
• Drowsiness and sedation — from effects on wakefulness centers
• Paresthesia — tingling sensations from effects on sensory nerve pathways
• Driving impairment — from combined effects on alertness, reaction time, and coordination

This is why the FDA requires the 8-hour driving restriction. It's not because Reyvow makes you feel sleepy — it's because it can impair driving ability even when you feel alert. For more on managing these effects, see our Reyvow side effects guide.

Why Does the Mechanism of Action Matter to Patients?

Understanding how Reyvow works isn't just academic. It has practical implications:

• If you have heart disease: Reyvow was one of the few acute migraine treatments that didn't carry cardiovascular vasoconstriction risk. With its discontinuation, talk to your doctor about CGRP-based alternatives, which also lack vasoconstriction effects.
• If you take antidepressants: Because Reyvow acts on serotonin receptors, combining it with SSRIs, SNRIs, or other serotonergic drugs increases the risk of serotonin syndrome. This is a direct consequence of its mechanism.
• If you need to drive: The 8-hour restriction is a direct result of how broadly 5-HT1F receptors are distributed in the brain.

The Bottom Line

Reyvow works by activating serotonin 5-HT1F receptors in the trigeminal pathway, calming overactive nerves and reducing the release of inflammatory chemicals that cause migraine pain. Its unique mechanism avoids the blood vessel narrowing that makes triptans risky for some patients — but it comes with CNS side effects and a strict driving restriction.

With Reyvow being permanently discontinued in 2026, patients who rely on it should work with their doctors to find alternative treatments. To learn more about Reyvow, read our complete guide to Reyvow uses and dosage. If you still need to fill a prescription, MedFinder can help you locate remaining pharmacy stock.