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Not all antihistamines are the same – and some…

Science · October 31, 2026 · The Conversation · 4 min

Some allergy tablets make you sleepy and slow your reactions, others barely affect you. Here’s why – and what to check before you buy.

<a class="source" href="https://www.shutterstock.com/image-photo/pills-blister-isolated-on-white-tablets-1447032746">Tatiana Yashina/Shutterstock</a> </figcaption> </figure>

<a href="https://theconversation.com/profiles/dipa-kamdar-1485027">Dipa Kamdar</a>, <a href="https://theconversation.com/institutions/kingston-university-949">Kingston University</a>

Millions of people take antihistamines for allergies, but some of these medicines can make you sleepy, slow your reactions and affect your concentration. Others are much less likely to have these effects. Knowing the difference can help you choose an allergy treatment that won’t interfere with your day.

Antihistamines work by <a href="https://www.ncbi.nlm.nih.gov/books/NBK538188/">blocking histamine</a>, a chemical released by the immune system during an allergic reaction. Histamine causes many common allergy symptoms, including itching, sneezing, watery eyes and a runny nose.

The first antihistamines were developed in the <a href="https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2222.1999.00004.x-i1?saml_referrer">1940s</a>. Medicines such as chlorphenamine, diphenhydramine and promethazine are known as <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC3667286/">first-generation antihistamines</a>, and they are still widely available in allergy medicines, cold remedies and sleep aids.

In the <a href="https://revistas.udes.edu.co/innovaciencia/en/article/view/3651">1980s and 1990s</a>, newer antihistamines such as loratadine, cetirizine and fexofenadine were introduced. Known as <a href="https://www.ccjm.org/content/ccjom/67/5/372.full.pdf">second-generation antihistamines</a>, they were designed to cause fewer side-effects, especially drowsiness.

The reason some antihistamines cause drowsiness while others do not comes down to what happens in the brain. Older antihistamines can easily cross the <a href="https://www.nature.com/articles/s41392-023-01481-w">blood-brain barrier</a>, which helps control what enters the brain from the bloodstream. There, they block histamine receptors that help keep you <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC3016451/">alert and awake</a>.

<a href="https://www.sciencedirect.com/science/article/pii/S0163725806001227?via%3Dihub#aep-section-id21">Brain imaging studies</a> show that older antihistamines block more histamine receptors in the brain than newer ones. This is linked to a greater risk of sleepiness, slower reaction times and difficulty concentrating.

Newer antihistamines generally have <a href="https://www.sciencedirect.com/science/article/pii/S0163725806001227?via%3Dihub#aep-section-id21">less effect</a> on the brain, although there are differences between medicines. One study found that fexofenadine occupied around 2% of histamine receptors in the brain, compared with 24% for cetirizine (a second-generation drug) and 50 to 60% for chlorpheniramine. This helps explain why some “non-drowsy” antihistamines may still cause sleepiness in certain people.

Researchers increasingly recognise that antihistamines do not fall neatly into two groups: those that cause sleepiness and those that do not. Instead, they are better viewed as existing on a spectrum.

Some older antihistamines have a strong effect on alertness; some newer medicines have a mild effect and others have very little effect on the brain at all. This is why two medicines that treat the same allergy symptoms can leave you feeling quite different.

Some people find the sedative effects useful. <a href="https://www.ncbi.nlm.nih.gov/books/NBK526010/">Diphenhydramine</a>, for example, is sold in several over-the-counter sleep aids. But feeling sleepy is not always harmless.

Antihistamines can affect attention, memory, coordination and reaction times. This can make activities such as <a href="https://www.ingentaconnect.com/content/ocean/aap/2001/00000022/00000005/art00003;jsessionid=40iw3p5rs5res.x-ic-live-03">driving or operating machinery</a> less safe. You may not realise how much you are affected: even if you feel only slightly tired, your reactions may be slower and your concentration poorer.

<figure class="align-center "> <img alt="A man yawning while driving." src="https://images.theconversation.com/files/768531/original/file-20261027-52-p3sqd5.jpg?ixlib=rb-4.1.1&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/768531/original/file-20261027-52-p3sqd5.jpg?ixlib=rb-4.1.1&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/768531/original/file-20261027-52-p3sqd5.jpg?ixlib=rb-4.1.1&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/768531/original/file-20261027-52-p3sqd5.jpg?ixlib=rb-4.1.1&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/768531/original/file-20261027-52-p3sqd5.jpg?ixlib=rb-4.1.1&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/768531/original/file-20261027-52-p3sqd5.jpg?ixlib=rb-4.1.1&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/768531/original/file-20261027-52-p3sqd5.jpg?ixlib=rb-4.1.1&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"> <figcaption> Some antihistamines can make you drowsy. <a class="source" href="https://www.shutterstock.com/image-photo/truck-driver-driving-on-highway-yawning-2504344099?trackingId=65870768-89a0-4f5c-a2cd-c8ebb2e0103e&listId=searchResults">Miguel Perfectti/Shutterstock.com</a> </figcaption> </figure>

For people who need regular allergy treatment, <a href="https://pubmed.ncbi.nlm.nih.gov/10748947/">newer antihistamines are generally recommended</a> because they are less likely to cause sleepiness. Some second-generation antihistamines, particularly cetirizine, can still cause drowsiness in some people, though the effect is usually less pronounced than with older medicines.

<h2>Not the only concern</h2>

Sleepiness is not the only concern with older antihistamines. Many also affect another chemical messenger in the body, giving them what are known as <a href="https://www.ncbi.nlm.nih.gov/books/NBK555893/">anticholinergic effects</a>.

As well as blocking histamine, these medicines block <a href="https://www.ncbi.nlm.nih.gov/books/NBK557825/">acetylcholine</a>, a chemical messenger that helps the brain control memory, learning and attention. It also plays a role in other functions throughout the body.

Newer antihistamines act more specifically on histamine receptors involved in allergic symptoms and have weaker acetylcholine effects. They are also less likely to enter the brain. As a result, they generally cause fewer unwanted effects than older antihistamines.

In the short term, medicines with anticholinergic effects can <a href="https://www.ncbi.nlm.nih.gov/books/NBK555893/">cause</a> dry mouth, blurred vision, constipation, dizziness and confusion. These effects can be more serious in <a href="https://pubmed.ncbi.nlm.nih.gov/11584981/">older people</a> and may raise the risk of <a href="https://pubmed.ncbi.nlm.nih.gov/35465815/">falls</a> resulting in an increasing likelihood of hospital stays and losing the ability to live independently.

Scientists have also explored whether medicines with anticholinergic effects, including first-generation antihistamines, could affect brain health. The <a href="https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2091745">research</a> hasn’t proved that these medicines directly caused dementia. But the findings have strengthened <a href="https://www.medscape.com/viewarticle/older-adults-advised-limit-anticholinergic-medicines-2026a1000pmy?form=fpf">advice</a> to avoid unnecessary use of anticholinergic medicines, especially among older people.

<h2>Why are older antihistamines still available?</h2>

Despite these concerns, older antihistamines remain widely available. Many people buy the same medicines they have used for years. Others <a href="https://pubmed.ncbi.nlm.nih.gov/12113226/">appreciate the sedative effects</a>, particularly when symptoms such as itching or hay fever interfere with sleep.

Older antihistamines can still be useful for treating allergies. But people who drive, who need to concentrate on studying or who take several other medicines may be better off with an option that is less likely to cause sleepiness.

Before choosing an allergy tablet, check which antihistamine it contains. Medicines that treat the same symptoms can have very different effects on how alert you feel, so the right choice can make a difference to your day.<img src="https://counter.theconversation.com/content/294819/count.gif?distributor=republish-lightbox-basic" alt="The Conversation" width="1" height="1" style="border: none !important; box-shadow: none !important; margin: 0 !important; max-height: 1px !important; max-width: 1px !important; min-height: 1px !important; min-width: 1px !important; opacity: 0 !important; outline: none !important; padding: 0 !important" referrerpolicy="no-referrer-when-downgrade" />

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