Diphenhydramine
Benadryl · Dramamine
First-Generation H1 Antagonist with Anticholinergic PropertiesGeneric availableTDM data
Diphenhydramine competitively antagonizes H1 histamine receptors, reducing allergic/inflammatory responses. Strong anticholinergic (muscarinic antagonism) and CNS-depressant properties. Sedation from CNS H1 antagonism and anticholinergic effects. Rapid onset IM/IV. In psychiatry: used for acute dystonia (rescue), insomnia, EPS treatment, though first-gen antihistamines increasingly avoided in elderly due to anticholinergic burden.
Compare Diphenhydramine →FDA-Approved Indications
- Allergic reactions and anaphylaxis adjunct (after acute symptoms controlled with epinephrine)
- Motion sickness
- Parkinsonism and drug-induced parkinsonism when oral therapy impossible/contraindicated
- Drug-induced EPS from antipsychotics
Common Off-Label Uses
- Insomnia (OTC use — not FDA-approved as prescription hypnotic)
- Acute dystonia rescue (IM 50 mg)
- Motion sickness
What Sets This Drug Apart
- First-generation antihistamine with strong anticholinergic and CNS-depressant properties — HIGH anticholinergic burden
- Rapid parenteral onset suitable for acute dystonia rescue (IM injection) and EPS reversal
- Absolute contraindication in neonates/premature infants and nursing mothers — safety concern in youngest and vulnerable populations
- Narrow-angle glaucoma contraindication — anticholinergic effects may precipitate angle closure
- Paradoxical excitation in young children (hallucinations, seizures, death in overdose) — unpredictable response
- Marked anticholinergic burden (dry mouth, constipation, urinary retention, confusion) — avoid with other anticholinergics; contraindicated in elderly per Beers Criteria