About one-third of people will experience motion sickness at some point. I won't. But if my wife is floating in a swimming pool and a malnourished leafhopper lands in the water, the resulting ripple is enough to turn her green.
Speaking of green, I coughed up plenty of it for a once-in-a-lifetime snorkeling trip to Hawaiʻi. Only to discover that snorkeling, one of my all-time favorite activities, made her seasick. And I'm not talking open ocean snorkeling. No, it was a well-protected cove with all the wave action of a birdbath.
Goodbye, Maldives. Hello, Arizona.
Motion sickness is one of those annoying problems that everyone understands because almost everyone has experienced it. Yet despite millions of miserable passengers, cruise ship customers, and airline travelers, drug development for motion sickness has barely budged since the 1970s. That would be fine if there were decent motion sickness drugs. There aren't. The existing armamentarium of medicines falls somewhere on the spectrum between "suck" and "really suck," and it has occupied that territory through Korea, Vietnam, Iraq, and Afghanistan. That's a lot of wars. And a lot of spewing.
Finally, something different
In 2025, the FDA approved tradipitant (Nereus), the first new prescription drug for motion sickness in more than 40 years. Surprisingly, the drug's mechanism isn't new at all. In fact, drugs that work exactly the same way have been around for more than twenty years.
Sucky and sleepy
The drugs most people reach for are Dramamine, Bonine (meclizine), or a scopolamine patch.
Their benefits are often modest, while their side effects—especially drowsiness, dry mouth, and blurred vision—are anything but, enabling you to spew while half-asleep (not yet a motor vehicle violation).
Dramamine and Bonine are antihistamines. Histamine isn't just something that causes itchy eyes during allergy season. In the brain, it also helps regulate alertness. So when you block histamine receptors to reduce motion sickness, you frequently accomplish something else.
You might fall asleep. Benadryl—an 80-year-old drug that somehow ended up being marketed for both insomnia and motion sickness—has the rare ability to disappoint at both: it doesn't reliably help you sleep when you want to, and it doesn't reliably keep you from puking when you need it to.
Scopolamine avoids histamine altogether by blocking muscarinic acetylcholine receptors, another important signaling pathway involved in balance and nausea. It's very effective for some, but not without an assorted combination of dry mouth, blurred vision, constipation, and confusion.
In other words, the older drugs don't just quiet the nausea centers. They also interfere with normal brain function.
A different target altogether
Tradipitant takes a completely different approach.
If you've never heard of substance P, you're not alone. It's a small signaling peptide involved in pain, inflammation, and, most importantly, vomiting. Ironically, the "P" has nothing to do with peptide [1], which will no doubt disappoint all the chuckleheads injecting experimental peptides in the never-ending quest to look like those little guys from Space Invaders.
During vomiting, substance P is one of the last chemical signals telling the brain, "It's time to get serious." Tradipitant blocks that signal before it reaches its destination. No message. No vomiting. At least that's the theory.
This may sound familiar
NK1 blockers have been used for years to prevent the severe nausea and vomiting caused by chemotherapy. Drugs such as aprepitant (Emend), fosaprepitant, netupitant, and rolapitant all belong to the same family. Yet despite their success, no one had seriously pursued the same approach for motion sickness until now. Apparently, someone finally realized that vomiting is vomiting.
How well does the stuff work?
It's not perfect, but still pretty impressive.
Tradipitant was evaluated in two randomized, double-blind, placebo-controlled Phase 3 trials involving 681 adults with a history of motion sickness. In one study, 44% of participants receiving placebo vomited during the boat trip, compared with 18% of those taking tradipitant. The second trial produced similar, if not better, results: 38% of placebo recipients vomited versus just 10% of those receiving the drug. Overall, the drug reduced the risk of vomiting by about two-thirds.
It won't keep your lunch down on a trip on the "Vomit Comet," but that's not half bad.
Bottom line: the wife assay
Personally, none of this means a thing unless I can get my wife to try Seven Mile Beach or Providenciales. Then I'll cheerfully stuff my fat ass into my woefully underused shorty and float my cares away.
NOTE:
[1] Duh, I know. "Substance P" is not actually an abbreviation. The peptide was named in 1931 after the powdered tissue extract ("preparation") from which it was first isolated. The name stuck because scientists, like everyone else, hate changing names once they've become established.
