Diphenhydramine

Mechanism of action

First-generation H1 histamine receptor antagonist

In plain language

Blocks histamine from triggering the sneezing, itching, and swelling of allergic reactions, and because it slips easily into the brain, it also brings on the drowsiness that's put to use as an over-the-counter sleep aid.

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ClinicalPlain language

How it works

Diphenhydramine is a first-generation ethanolamine-class H1-receptor antagonist that competitively blocks histamine at peripheral H1 receptors, reducing the capillary permeability, vasodilation, and smooth-muscle stimulation responsible for allergic symptoms. Its high lipophilicity lets it readily cross the blood-brain barrier and antagonize central H1 receptors, producing sedation, while concurrent anticholinergic activity accounts for its efficacy against motion-sickness-induced nausea and drug-induced extrapyramidal symptoms. Peak plasma levels occur roughly 1-4 hours after an oral dose, with a half-life of about 4-8 hours. Together, these antihistaminic, anticholinergic, and CNS-depressant effects explain its labeled uses across allergy relief, antiemetic therapy, adjunctive parkinsonism treatment, and short-term insomnia.

Therapeutic applications

FDA-labeled for symptomatic relief of allergic conditions and upper respiratory allergy and common-cold symptoms; adjunctive therapy in anaphylactic reactions after epinephrine, and treatment of allergic reactions to blood or plasma (injectable form); active and prophylactic treatment of motion sickness; treatment of parkinsonism, including drug-induced extrapyramidal reactions, when oral anticholinergic therapy is impractical; and short-term management of occasional insomnia as a nighttime sleep aid.

Class

Small molecule

Therapeutic area

Allergy / Immunology

Source

PubChem CID 3100 ↗FDA label (DailyMed) ↗