What is the mechanism of action of Diphenhydramine (Benadryl) and which receptors does it affect?

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From the Guidelines

Benadryl (diphenhydramine) primarily works by blocking histamine H1 receptors in the body, and it also has anticholinergic effects by blocking muscarinic acetylcholine receptors, contributing to its sedative properties and dry mouth side effects. The mechanism of action of Benadryl involves the blockade of histamine H1 receptors, which prevents histamine from attaching and triggering allergic symptoms like itching, sneezing, and runny nose 1. Beyond its antihistamine effects, Benadryl also affects serotonin receptors and can cross the blood-brain barrier, explaining its sedative effects and use as a sleep aid 1. Some key points to consider when using Benadryl include:

  • The standard adult dose is 25-50mg every 4-6 hours, with a maximum of 300mg daily.
  • Children's dosing is weight-based and should be carefully calculated.
  • Due to its sedative effects, users should avoid driving or operating machinery after taking Benadryl.
  • The medication typically takes 15-30 minutes to begin working and lasts for 4-6 hours.
  • These multiple receptor interactions explain why Benadryl is effective for allergies but also causes drowsiness, dry mouth, and other anticholinergic side effects 1. It's also worth noting that Benadryl has been used in various clinical settings, including as an adjunct for sedation in endoscopic procedures, and its effects have been studied in relation to other medications and conditions, such as anaphylaxis and mast cell activation syndrome 1.

From the Research

Mechanism of Action of Benadryl

  • Benadryl, also known as diphenhydramine, is an antihistamine that acts as an antagonist to the histamine receptors in the body.
  • The drug primarily targets the H1 receptor, which is one of the four G-protein-coupled receptors that mediate the effects of histamine 2.
  • By blocking the H1 receptor, Benadryl inhibits the action of histamine, a neurotransmitter involved in various physiological processes such as alertness, wakefulness, and immune responses.

Receptors Affected by Benadryl

  • The primary receptor affected by Benadryl is the H1 receptor, which is a postsynaptic receptor in the brain that mediates many of the central effects of histamine 2.
  • The H1 receptor is involved in regulating alertness and wakefulness, and blocking this receptor can lead to drowsiness and sedation.
  • While Benadryl may also have some affinity for other histamine receptors, such as the H2, H3, and H4 receptors, its primary mechanism of action is through the blockade of the H1 receptor 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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