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Why can diphenhydramine and promethazine be used for motion sickness?

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antihistamines, including Benadryl — antihistamine Antihistamines such as Benadryl (diphenhydramine) and Claritin (loratadine) can be purchased without prescriptions. Both of those agents act by blocking H₁ receptors. However, whereas Benadryl binds to those receptors in the central nervous system (CNS), causing drowsiness, Claritin does not readily enter the CNS and thus does not normally cause drowsiness.

Diphenhydramine and promethazine are categorized as H1 receptor antagonists, a group of drugs that selectively counteract the effects of histamine. While their primary use is to alleviate allergic symptoms, their specific action on the central nervous system makes them effective in the prevention and treatment of motion sickness.1

These older antihistamines are effective for motion sickness because they bind strongly to H1 receptors within the brain. Additionally, they bind to muscarinic receptors in the brain, an action that is believed to contribute to their therapeutic benefit in mitigating the nausea and vomiting associated with motion-induced sensory conflict. Because these drugs possess sedative properties, they are often associated with drowsiness, which is a common side effect of their use.21