Why are antihistamines used for nausea and vomiting?

October 14, 2025 •

4 min read

According to the American Gastroenterological Association, antihistamines and anticholinergics are recommended for treating nausea caused by vestibular issues like vertigo and motion sickness. This powerful anti-nausea effect begs the question: why are antihistamines used for nausea and vomiting?

Quick Summary

First-generation antihistamines effectively combat nausea and vomiting by blocking histamine and acetylcholine receptors in the brain's vomiting center and inner ear. Their ability to cross the blood-brain barrier makes them particularly useful for motion sickness and vertigo.

Key Points

Vestibular Pathway Blockade: Antihistamines counteract nausea by blocking the histamine- and acetylcholine-mediated signals from the inner ear's balance system to the brain's vomiting center.
First-Generation's Central Action: Only first-generation antihistamines, such as meclizine and dimenhydrinate, are effective for nausea because they can cross the blood-brain barrier.
Specific Indications: Antihistamines are most effective for vestibular-related issues like motion sickness and vertigo, as well as some forms of pregnancy-related nausea.
Side Effects: The most common side effects include drowsiness and anticholinergic effects like dry mouth and blurred vision due to their central nervous system activity.
Not a Universal Cure: Because nausea can originate from different pathways, antihistamines are not suitable for all types of nausea and vomiting, such as that caused by chemotherapy or GI irritation.
Prophylactic Use: For motion sickness, antihistamines work best when taken before symptoms appear to prevent stimulation of the vomiting center.

The Neurobiological Basis of Nausea

To understand why antihistamines help with nausea, it's crucial to know how the body generates the sensation of wanting to vomit. The vomiting reflex is controlled by the vomiting center in the brainstem. This center can be activated by several different pathways, which is why different types of nausea respond to different medications.

One of the primary pathways involves the vestibular system, the sensory network in the inner ear that helps regulate balance and spatial orientation. When the vestibular system receives confusing or conflicting signals—such as during motion sickness—it can send signals via neurotransmitters like histamine and acetylcholine to the vomiting center. For example, motion sickness occurs when there is a mismatch between the visual information your eyes see and the movement sensed by your inner ear.

Another pathway is the chemoreceptor trigger zone (CTZ), which monitors the blood for toxins and drugs that may need to be expelled. The CTZ is rich in receptors for dopamine and serotonin, which is why medications targeting these receptors are used for chemotherapy-induced nausea. The antihistamines that treat motion sickness primarily work on the vestibular pathway rather than the CTZ.

Mechanism of Action: Blocking the Signals

The effectiveness of antihistamines as antiemetics stems from their specific pharmacological actions on the central nervous system (CNS). However, this ability is primarily limited to first-generation antihistamines.

H1 Receptor Blockade

Histamine's Role: Histamine acts as a neurotransmitter in the brain, and H1 receptors are present in the vestibular nuclei, which are part of the balance system. When the inner ear is overstimulated, it can release histamine, activating these H1 receptors and triggering nausea.
Antihistamine Action: First-generation antihistamines work as H1 receptor antagonists, meaning they block the action of histamine at these receptors. By preventing histamine from binding, they reduce the signaling to the vomiting center, thereby alleviating nausea.

Anticholinergic Properties

Acetylcholine's Role: Many first-generation antihistamines also possess anticholinergic properties, meaning they inhibit the action of acetylcholine at muscarinic receptors. Acetylcholine is another key neurotransmitter involved in transmitting signals from the vestibular system to the vomiting center.
Dual Blockade: This dual action—blocking both histamine (H1) and acetylcholine (muscarinic) receptors—provides a potent calming effect on the vestibular system. This makes first-generation antihistamines highly effective for motion-induced nausea and vertigo.

Why Newer Antihistamines Don't Work for Nausea

In contrast to first-generation drugs like diphenhydramine (Benadryl) and meclizine (Antivert), newer, second-generation antihistamines (like loratadine and cetirizine) are ineffective for nausea. The key difference lies in their chemical structure, which prevents them from crossing the blood-brain barrier into the central nervous system. Their action is limited to H1 receptors in the periphery, which is sufficient for treating allergies but not for controlling the vestibular-mediated nausea that originates in the brain.

Applications for Nausea and Vomiting

First-generation antihistamines are used in several clinical scenarios for their antiemetic effects:

Motion Sickness: For those prone to car, sea, or air sickness, a medication like dimenhydrinate (Dramamine) or meclizine can be highly effective. These should be taken before travel begins to pre-emptively desensitize the inner ear and block the signals that cause motion sickness.
Vertigo: Meclizine is often prescribed for vertigo, a condition where people experience a sensation of spinning or dizziness, typically caused by inner ear problems. By suppressing the vestibular system, it helps to alleviate the associated dizziness and nausea.
Pregnancy-Related Nausea: Doxylamine, an antihistamine, is often combined with vitamin B6 (pyridoxine) as a first-line treatment for nausea and vomiting in pregnancy, commonly known as morning sickness. This combination is a category A medication during pregnancy, indicating a low risk of fetal harm.

Antihistamines vs. Other Antiemetics

The choice of antiemetic depends heavily on the root cause of the nausea. Below is a comparison of different antiemetic classes to illustrate the specific role of antihistamines.


Drug Class	Mechanism of Action	Best For	Common Side Effects	First-Gen Antihistamine Examples
First-Gen Antihistamines	Blocks H1 receptors and muscarinic acetylcholine receptors.	Motion sickness, vertigo, some morning sickness.	Sedation, dry mouth, blurred vision, dizziness.	Meclizine, Dimenhydrinate, Diphenhydramine.
Serotonin (5-HT3) Antagonists	Blocks serotonin at 5-HT3 receptors in the intestines and chemoreceptor trigger zone.	Chemotherapy-induced and postoperative nausea and vomiting.	Headache, diarrhea, fatigue, QT prolongation.	Ondansetron (Zofran), Granisetron.
Dopamine Antagonists	Blocks dopamine receptors in the CTZ.	Postoperative nausea, migraine-associated nausea.	Sedation, extrapyramidal symptoms, low blood pressure.	Promethazine, Metoclopramide.

Side Effects and Important Considerations

While effective, first-generation antihistamines come with a notable side effect profile, primarily due to their ability to cross the blood-brain barrier. The most well-known side effect is drowsiness or sedation, which can impair judgment and coordination. For this reason, anyone taking these medications should avoid driving or operating heavy machinery until they know how they will be affected.

Other common side effects stem from their anticholinergic activity and include:

Dry mouth
Constipation
Blurred vision
Dizziness
Difficulty urinating

Long-term use is not typically recommended, and older adults are at a higher risk of adverse effects, including a higher risk of falls. Always consult a healthcare professional before starting or stopping any medication.

Conclusion

In summary, first-generation antihistamines are used for nausea and vomiting because of their dual mechanism of blocking both histamine and acetylcholine pathways that originate in the vestibular system. This makes them particularly effective for conditions like motion sickness and vertigo. Their ability to cross the blood-brain barrier, which is also responsible for side effects like drowsiness, is the key to their antiemetic action for these specific types of nausea. However, for other causes of nausea, such as chemotherapy, other classes of medications that target different pathways are more appropriate. Understanding the specific mechanism allows for targeted, effective treatment while managing the potential side effects associated with their use.

Frequently Asked Questions

Only first-generation antihistamines, such as meclizine (Antivert, Bonine), dimenhydrinate (Dramamine), and diphenhydramine (Benadryl), are used for nausea. They can cross the blood-brain barrier to act on the central nervous system, where they block signals from the inner ear that cause nausea.

Second-generation antihistamines, like cetirizine (Zyrtec) or loratadine (Claritin), are not effective for nausea because their chemical structure prevents them from crossing the blood-brain barrier. Therefore, they cannot block the histamine receptors in the brain and inner ear that cause motion sickness and vertigo.

Yes, Benadryl (diphenhydramine) is a first-generation antihistamine with antiemetic properties that can be used for nausea, particularly that associated with motion sickness and vertigo. Its antiemetic effects are due to its ability to block H1 and muscarinic receptors in the brain.

First-generation antihistamines cause drowsiness because they can easily cross the blood-brain barrier. Histamine is a neurotransmitter in the brain that plays a role in keeping you awake, so by blocking H1 receptors, these medications cause sedation.

Yes, there are several other classes of antiemetics. These include serotonin antagonists (e.g., ondansetron for chemotherapy and post-operative nausea), dopamine antagonists (e.g., promethazine for various causes), and anticholinergics (e.g., scopolamine for motion sickness).

Doxylamine, an antihistamine, is combined with vitamin B6 (pyridoxine) as a first-line treatment for morning sickness, and this combination is generally considered safe. However, other antihistamines may carry risks, and you should always consult a doctor before taking any medication during pregnancy.

Antihistamines treat the nausea and dizziness of vertigo by suppressing the vestibular system in the inner ear. They block the signals involving histamine and acetylcholine that cause the sensation of spinning and imbalance.

For maximum effectiveness against motion sickness, you should take antihistamines, such as dimenhydrinate or meclizine, before traveling. They are most effective when used proactively to prevent symptoms rather than treat them once they begin.