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Structural formula
Structural formula of diphenhydramine
Non-proprietary name Diphenhydramine
other names
  • 2-Benzhydryloxy- N , N -dimethyl-ethylamine ( IUPAC )
  • Latin : Diphenhydramini hydrochloridum
Molecular formula
External identifiers / databases
CAS number
  • 58-73-1
  • 147-24-0 (hydrochloride)
EC number 200-396-7
ECHA InfoCard 100,000,360
PubChem 3100
DrugBank DB01075
Wikidata Q413486
Drug information
ATC code
Drug class

Antihistamines , psychotropic

Mechanism of action
Molar mass 255.36 g mol −1
Physical state



1.02 g cm −3 (20 ° C)

Melting point

168–172 ° C (hydrochloride)

boiling point

150–165 ° C (approx. 300 Pa )

pK s value



poor in water (3 g l −1 at 37 ° C)

Refractive index


safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning


H and P phrases H: 302
P: no P-phrases
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Diphenhydramine ( DPH for short , sometimes DHM ) is a drug from the class of H1 antihistamines . At the same time, it has a strong anticholinergic effect and also inhibits the reuptake of serotonin in the brain.

Diphenhydramine was previously used in the therapy of allergies ; Today, however, it is only used in Germany as a sedative and for nausea and vomiting. In North America, diphenhydramine is still widely used as an antiallergic agent in addition to its use as a sleeping and sedative in a different dose recommendation. Diphenhydramine also has FDA approval for the symptomatic treatment of Parkinson's and extrapyramidal dyskinesia .

In Germany, Austria and Switzerland, the dispensing of diphenhydramine is subject to pharmacy requirements , but in Germany it is also subject to a prescription if it is to be prescribed for parenteral use.



Diphenhydramine is well and quickly absorbed into the bloodstream. The oral bioavailability is about 50%. The highest concentration in the blood is measured after about an hour, the plasma half-life is between 4 and 6 hours. Diphenhydramine is mainly metabolized in the liver by the cytochrome P450 type CYP2D6 via the route of N - demethylation . The metabolites are largely excreted by the renal route, i.e. via the kidneys with the urine.

Mechanism of action

As a competitive antagonist, diphenhydramine inhibits the action of histamine on H 1 receptors . Because of this effect, antiallergic , antiemetic and sedating effects can be observed at a therapeutic dose of 25–50 mg . Diphenhydramine also shows a high affinity for muscarinic receptors and thus has a specific anticholinergic component, which is why diphenhydramine is also used in the USA for the symptomatic treatment of Parkinson's and extrapyramidal dyskinesias . It is also a non-selective serotonin reuptake inhibitor , which results in an antidepressant active component. For the modern antidepressants (selective serotonin reuptake inhibitors), especially fluoxetine , diphenhydramine was the starting material for development. Diphenhydramine also has an effect on opioid receptors , which can lead to an intensification of the effect when taking opioids .

Overview of binding sites and effects of diphenhydramine
receptor Mode of action effect
H 1 receptor (peripheral) Inverse agonist Antiallergic
H 1 receptor (brain) antagonist Sedation
Muscarinic acetylcholine receptor M 1 , M 2 , M 3 , M 4 , M 5 antagonist Anti-Parkinson, anti-extrapyramidal , anticholinergic
Na channels Blockers Local anesthetic
Serotonin transporters Reuptake inhibitors Mood- brightening, anti-obsessive (= compulsorily releasing)
μ, δ, κ opioid receptors Enhancement of the morphine effect analgesia

Side effects

Fatigue can almost always be observed when taking diphenhydramine. Dry mouth, photophobia and visual disturbances can also occur. Patients with narrow-angle glaucoma and those with urination problems should avoid diphenhydramine as it exacerbates these symptoms. The same applies to patients with congenital long QT syndrome , since the QT interval in the ECG can be dangerously prolonged by diphenhydramine with the appropriate predisposition.


MAO inhibitors lead to a slower breakdown of diphenhydramine and to overdosing with repeated use. The effect of diphenhydramine is also increased by other anticholinergics , central depressant drugs and ethanol .

Emergency medicine

As a histamine antagonist , diphenhydramine HCl is used under the name of dibondrin for symptomatic anaphylactic reactions (stage 1–3).

Other indications

Due to its ability to cross the blood-brain barrier and its specific effects on various messenger substances in the brain, diphenhydramine is also used as an off-label medication in neurology and psychiatry , e.g. B. Parkinson's (approved in the US for this indication) and obsessive-compulsive disorder .

Diphenhydramine as a hallucinogen

The intake of diphenhydramine can also have a hallucinogenic effect, which is especially the case with larger doses above the therapeutic range of 200 mg. The effects of delirious intoxication are similar to those of nightshade plants [z. B. Atropine ( rac - hyoscyamine )]. At high doses, there may be a total loss of reality. Diphenhydramine is also consumed in combination with dextromethorphan for intoxication purposes.

Presentation and extraction

Diphenhydramine is synthesized by the etherification of bromodiphenylmethane with N , N- dimethylethanolamine in the presence of potassium carbonate .

Synthesis of diphenhydramine

Trade names


Abopretten (D), Benadryl (DK), Benocten (CH), Betadorm (D), Bonox (CH), Calmaben (A), Dibondrin (A), Docpelin Nachtsterne (D), Dolestan (D), Dorm (D) , Dormutil (D), Emesan (D), Halbmond (D), Hevert-Dorm (D), Hemodorm (D), Moradorm (D), Nardyl (CH), Nautamine (VN), Nervo OPT (D), Noctor (A), Olidon (D), Sediat (D), Sodormwell (D), Vivinox Sleep (D)

Combination preparations

Anaesthecomp (D), Apozema Insecticum (A), Benylin (CH), Coldistan (A), DayNight (D), Detensor (CH), Histaderm (A), Lunadon (CH), Makatussin Comp (CH), Multodrin (A ), Parapic (CH), Pruristop (A), Rhinitin (CH), Rhinodrin (A), Somnium (CH), Sunsan (A), Tossamin plus (CH), Zantall (A)

Web links

Commons : Diphenhydramine  - Collection of Pictures, Videos and Audio Files

Individual evidence

  1. a b c d Entry on diphenhydramine. In: Römpp Online . Georg Thieme Verlag, accessed on July 7, 2014.
  2. a b Entry on diphenhydramine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  3. a b data sheet Diphenhydramine hydrochloride from Sigma-Aldrich , accessed on March 28, 2011 ( PDF ).
  4. a b c d e f g h i j A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications. 4th edition. Thieme-Verlag, Stuttgart 2001, ISBN 1-58890-031-2 .
  5. Entry on diphenhydramine in Flexikon , a wiki of the DocCheck company , accessed on May 2, 2013.
  6. a b C. Bolden, B. Cusack, E. Richelson: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. In: The Journal of pharmacology and experimental therapeutics. Volume 260, Number 2, February 1992, pp. 576-580, PMID 1346637 .
  7. Teppei Tanaka, Akira Takasu, Aihide Yoshino, Keiko Terazumi, Makoto Ide, Soichiro Nomura, Toshihisa Sakamoto: Diphenhydramine overdose mimicking serotonin syndrome. In: Psychiatry and Clinical Neurosciences. 65, 2011, p. 534, doi: 10.1111 / j.1440-1819.2011.02234.x .
  8. Joachim Framm et al.: Drug profiles . Deutscher Apotheker Verlag, 2009, ISBN 978-3-7692-4869-2 .
  9. National Institute of Health of the USA: Diphenhydramine , accessed August 11, 2013.
  10. Otto Benkert, Hanns Hippius: Compendium of Psychiatric Pharmacotherapy. 8th edition. Springer, 2011, ISBN 978-3-642-13043-4 .
  11. ^ Edward F. Domino: History of Modern Psychopharmacology. In: Psychosomatic Medicine. 61, 1999, pp. 591-598.
  12. ^ Joseph A. Lieberman: History of the Use of Antidepressants in Primary Care. In: Primary Care Companion J Clin Psychiatry. 2003; 5.
  13. A. Carlsson, M. Linqvist: Central and peripheral monoaminergic membrane-pump blockade by some addictive analgesics and anti-histamines. In: J Pharm Pharmacol . 21, 1969, pp. 460-464.
  14. DT Wong, FP Bymaster, EA Engleman: Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication. In: Life Sci . 57, 1995, pp. 411-441.
  15. ^ JH Biel: Some rationales for the development of antidepressant drugs. Molecular modification in drug design. In: Adv Chem. 45, 1964, pp. 114-139.
  16. KD Carr, JM Hiller, EJ Simon: Diphenhydramine potentiates narcotic but not endogenous opioid analgesia. In: Neuropeptides. 5 (4-6), Feb 1985, 411-414. doi: 10.1016 / 0143-4179 (85) 90041-1 . PMID 2860599
  17. Matthias Bastigkeit, Claudia Fellerer, Jürgen Grassl, Harald Gruber, Mario Krammel, Elisabeth Thurner-Petrick: Pharmacology and general emergency skills for the rescue service. ISBN 3-7089-0683-7 , p. 219.
  18. ^ Roger C. Duvoisin, Jacob Sage: Parkinson's Disease. A Guide for Patient and Family. Philadelphia 2001, pp. 60f.
  19. ^ Richard P. Swinson et al.: Obsessive Compulsive Disorder. New York 1998, pp. 315f.
  20. WA Hewlett, S. Vinogradov, WS Agras: Clomipramine, clonazepam, and clonidine treatment of obsessive-compulsive disorder. In: J Clin Psychopharmacol . 12 (6), Dec 1992, pp. 420-430.
  21. José A. Yaryura-Tobias, Fugen A. Neziroglu: Obsessive-Compulsive Disorder Spectrum: Pathogenesis, Diagnosis, and Treatment. Washington 1997, pp. 40f.
  22. On drug through pharmaceuticals. In: Pharmaceutical newspaper. 02/2006, accessed on August 11, 2013.