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Diphenhydramine

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Diphenhydramine

Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particularly at higher doses. This may manifest as agitation, anxiety, or restlessness rather than sedation. It is a first-generation H1-antihistamine and it works by blocking certain effects of histamine, which produces its antihistamine and sedative effects. Diphenhydramine is also a potent anticholinergic. It is mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremors in parkinsonism, and nausea. It is taken by mouth, injected into a vein, injected into a muscle, or applied to the skin. Maximal effect is typically around two hours after a dose, and effects can last for up to seven hours. Common side effects include sleepiness, poor coordination, and an upset stomach. There is no clear risk of harm when used during pregnancy; however, use during breastfeeding is not recommended. It was developed by George Rieveschl and put into commercial use in 1946. It is available as a generic medication. In 2023, it was the 294th most commonly prescribed medication in the United States, with more than 700,000 prescriptions. Its sedative and deliriant effects have led to some cases of recreational use.

Infobox

Pronunciation
/ˌdaɪfɛnˈhaɪdrəmiːn/ ⓘ
Trade names
Benadryl, others
AHFS/Drugs.com
Monograph
MedlinePlus
a682539
License data
mw- US DailyMed: Diphenhydramine
Pregnancycategory
AU: A
Dependenceliability
Low
Routes ofadministration
By mouth, intramuscular, intravenous, topical, rectal
Drug class
First-generation antihistamine, antimuscarinic, hallucinogen (deliriant)
ATC code
D04AA32 (WHO) D04AA33 (WHO), R06AA02 (WHO)
Legal status
AU: S4 (Prescription only) / S2 (Pharmacy Medicine) / S3 (Pharmacist Only Medicine) CA: OTC UK: P (Pharmacy medicines) US: OTC / Rx-only UN: Unscheduled
Bioavailability
40–60%
Protein binding
98–99%
Metabolism
Liver (CYP2D6, others)
Elimination half-life
Range: 2.4–13.5 h
Excretion
Urine: 94%Feces: 6%
CAS Number
58-73-1 Y
PubChem CID
3100
IUPHAR/BPS
1224
DrugBank
DB01075 Y
ChemSpider
2989 Y
UNII
8GTS82S83M
KEGG
D00300 N
ChEBI
CHEBI:4636 Y
ChEMBL
ChEMBL657 Y
CompTox Dashboard (EPA)
DTXSID4022949
ECHA InfoCard
100.000.360
Formula
C17H21NO
Molar mass
255.361 g·mol−1
3D model (JSmol)
Interactive image

Tables

Diphenhydramine[61] · Pharmacology › Pharmacodynamics
SERTTooltip Serotonin transporter
SERTTooltip Serotonin transporter
Site
SERTTooltip Serotonin transporter
Ki (nM)
3800+
Species
Human
NETTooltip Norepinephrine transporter
NETTooltip Norepinephrine transporter
Site
NETTooltip Norepinephrine transporter
Ki (nM)
960–2400
Species
Human
DATTooltip Dopamine transporter
DATTooltip Dopamine transporter
Site
DATTooltip Dopamine transporter
Ki (nM)
1100–2200
Species
Human
5-HT2C
5-HT2C
Site
5-HT2C
Ki (nM)
780
Species
Human
α1B
α1B
Site
α1B
Ki (nM)
1300
Species
Human
α2A
α2A
Site
α2A
Ki (nM)
2900
Species
Human
α2B
α2B
Site
α2B
Ki (nM)
1600
Species
Human
α2C
α2C
Site
α2C
Ki (nM)
2100
Species
Human
D2
D2
Site
D2
Ki (nM)
20000
Species
Rat
H1
H1
Site
H1
Ki (nM)
9.6–16
Species
Human
H2
H2
Site
H2
Ki (nM)
100000+
Species
Canine
H3
H3
Site
H3
Ki (nM)
10000+
Species
Human
H4
H4
Site
H4
Ki (nM)
10000+
Species
Human
M1
M1
Site
M1
Ki (nM)
80–100
Species
Human
M2
M2
Site
M2
Ki (nM)
120–490
Species
Human
M3
M3
Site
M3
Ki (nM)
84–229
Species
Human
M4
M4
Site
M4
Ki (nM)
53–112
Species
Human
M5
M5
Site
M5
Ki (nM)
30–260
Species
Human
VGSCTooltip Voltage-dependent sodium channel
VGSCTooltip Voltage-dependent sodium channel
Site
VGSCTooltip Voltage-dependent sodium channel
Ki (nM)
48000–86000
Species
Rat
hERGTooltip Human Ether-à-go-go-Related Gene
hERGTooltip Human Ether-à-go-go-Related Gene
Site
hERGTooltip Human Ether-à-go-go-Related Gene
Ki (nM)
27100 (IC50Tooltip Half-maximal inhibitory concentration)
Species
Human
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.
Site
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.
Site
Ki (nM)
Species
Ref
SERTTooltip Serotonin transporter
3800+
Human
NETTooltip Norepinephrine transporter
960–2400
Human
DATTooltip Dopamine transporter
1100–2200
Human
5-HT2C
780
Human
α1B
1300
Human
α2A
2900
Human
α2B
1600
Human
α2C
2100
Human
D2
20000
Rat
H1
9.6–16
Human
H2
100000+
Canine
H3
10000+
Human
H4
10000+
Human
M1
80–100
Human
M2
120–490
Human
M3
84–229
Human
M4
53–112
Human
M5
30–260
Human
VGSCTooltip Voltage-dependent sodium channel
48000–86000
Rat
hERGTooltip Human Ether-à-go-go-Related Gene
27100 (IC50Tooltip Half-maximal inhibitory concentration)
Human
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.
Overview of diphenhydramine targets and effects · Pharmacology › Pharmacodynamics
H1 receptor
H1 receptor
Biological target
H1 receptor
Mode of action
Inverse agonist
Effect
Allergy reduction; Sedation
mACh receptors
mACh receptors
Biological target
mACh receptors
Mode of action
Antagonist
Effect
Anticholinergic; Antiparkinson
Sodium channels
Sodium channels
Biological target
Sodium channels
Mode of action
Blocker
Effect
Local anesthetic
Biological target
Mode of action
Effect
H1 receptor
Inverse agonist
Allergy reduction; Sedation
mACh receptors
Antagonist
Anticholinergic; Antiparkinson
Sodium channels
Blocker
Local anesthetic

References

  1. Substance Abuse in the Mentally and Physically Disabled
    https://books.google.com/books?id=MY1kFYk98mQC&pg=PA26
  2. Neurology. Clinical Practice
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874453
  3. (emc)
    https://www.medicines.org.uk/emc/product/1476/smpc
  4. DailyMed
    https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=921b9f64-1096-46db-866a-67f0f9ff6790
  5. Clinical Pharmacokinetics
    https://doi.org/10.2165%2F00003088-198510060-00002
  6. AHFS Drug Information
    https://books.google.com/books?id=WR0NAQAAMAAJ
  7. Journal of Clinical Pharmacology
    https://doi.org/10.1002%2Fj.1552-4604.1990.tb01871.x
  8. American Pharmacy
    https://doi.org/10.1016%2Fs0095-9561%2816%2938634-0
  9. Sleep Med Rev
    https://doi.org/10.1016%2Fj.smrv.2008.08.001
  10. "Showing Diphenhydramine (DB01075)"
    http://www.drugbank.ca/drugs/DB01075
  11. FDA.gov
    https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017024s045lbl.pdf
  12. Journal of Clinical Psychopharmacology
    https://doi.org/10.1097%2F00004714-199206000-00013
  13. Drugs.com
    https://www.drugs.com/monograph/diphenhydramine-hydrochloride.html
  14. Lexicon of Psychiatry, Neurology, and the Neurosciences
    https://books.google.com/books?id=ea_QVG2BFy8C&pg=PA332
  15. Drugs.com
    https://www.drugs.com/pregnancy/diphenhydramine.html
  16. Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and Organic Compounds
    https://books.google.com/books?id=YTeY9ZEfNccC&pg=PA225
  17. Ohio History Central
    http://ohiohistorycentral.org/w/Benadryl?rec=2591
  18. ClinCalc
    https://clincalc.com/DrugStats/Top300Drugs.aspx
  19. ClinCalc
    https://clincalc.com/DrugStats/Drugs/Diphenhydramine
  20. Journal of Psychopharmacology
    https://doi.org/10.1177%2F0269881107083809
  21. Drugs.com
    https://www.drugs.com/monograph/diphenhydramine-hydrochloride.html
  22. Current Psychiatary
    https://web.archive.org/web/20130514183445/http://stg.currentpsychiatry.com/pdf/1112/1112CP_Freudenreich.pdf
  23. Postgraduate Medicine
    https://doi.org/10.3810%2Fpgm.1999.08.650
  24. Drugs.com
    https://www.drugs.com/monograph/diphenhydramine-hydrochloride.html
  25. Allergy and Asthma Proceedings
    https://doi.org/10.2500%2Faap.2007.28.3015
  26. CURRENT Diagnosis and Treatment Emergency Medicine
  27. The Cochrane Database of Systematic Reviews
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517288
  28. MedlinePlus
    https://medlineplus.gov/druginfo/meds/a601044.html
  29. Basic & Clinical Pharmacology
  30. "Benadryl Addiction"
    https://web.archive.org/web/20140104053402/http://allergies.emedtv.com/benadryl/benadryl-addiction.html
  31. The Journal of Pediatrics
    https://doi.org/10.1016%2FS0022-3476%2898%2970240-9
  32. The Telegraph
    https://www.telegraph.co.uk/travel/family-holidays/is-it-ok-drug-babies-toddlers-children-sleep-flight-antihistamines/
  33. BBC News
    https://www.bbc.com/news/magazine-21977785
  34. "If It Were My Child: No Benadryl for the Plane"
    https://web.archive.org/web/20210225070641/https://seattlemamadoc.seattlechildrens.org/if-it-were-my-child-no-benadryl-for-the-plane/
  35. J Clin Sleep Med
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5263087
  36. Lancet
    https://doi.org/10.1016%2FS0140-6736%2822%2900878-9
  37. American Family Physician
    https://www.aafp.org/pubs/afp/issues/2004/0301/p1169.html
  38. "Does Benadryl help with or cause anxiety?"
    https://www.drugs.com/medical-answers/benadryl-help-cause-anxiety-3574583/
  39. "Hydroxyzine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retri
  40. Genes, Brain and Behavior
    https://doi.org/10.1111%2Fj.1601-183X.2007.00316.x
  41. The Cochrane Database of Systematic Reviews
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289707
  42. StatPearls
    https://www.ncbi.nlm.nih.gov/books/NBK526010/
  43. "Diphenhydramine Side Effects"
    https://www.drugs.com/sfx/diphenhydramine-side-effects.html
  44. Meyler's Side Effects of Cardiovascular Drugs
    https://books.google.com/books?id=oeBgU3UwgZkC&dq=Diphenhydramine+QT+prolongation&pg=PA623
  45. Contact Dermatitis
    https://doi.org/10.1111%2Fj.1600-0536.1996.tb02402.x
  46. Journal of the American Academy of Dermatology
    https://doi.org/10.1016%2FS0190-9622%2883%2970024-1
  47. CNS Spectrums
    https://doi.org/10.1017%2Fs109285290001628x
  48. National Institute of Neurological Disorders and Stroke
    https://www.ninds.nih.gov/health-information/disorders/restless-legs-syndrome
  49. BMC Geriatrics
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377853
  50. American Family Physician
    https://pubmed.ncbi.nlm.nih.gov/11456429
  51. Drugs and Lactation Database (LactMed) Internet
    https://pubmed.ncbi.nlm.nih.gov/30000938
  52. Choosing Wisely: an initiative of the ABIM Foundation
    https://aahpm.org/uploads/about/3.6.1._AAHPM_5_Things_-_Choosing_Wisely.pdf
  53. Diphenhydramine Toxicity
    https://pubmed.ncbi.nlm.nih.gov/32491510
  54. MedlinePlus Medical Encyclopedia
    https://www.medlineplus.gov/ency/article/002636.htm
  55. Goodman & Gilman's The Pharmacological Basis of Therapeutics
  56. Poisoning & Drug Overdose
    http://www.accessmedicine.com/content.aspx?aID=55974020.
  57. The Journal of Pharmacology and Experimental Therapeutics
    https://doi.org/10.1016%2FS0022-3565%2824%2938031-0
  58. Pediatric Emergency Care
    https://doi.org/10.1097%2FPEC.0b013e31823b0e47
  59. "Diphenhydramine and Alcohol / Food Interactions"
    https://www.drugs.com/food-interactions/diphenhydramine.html
  60. Alcohol and Alcoholism
    https://doi.org/10.1093%2Falcalc%2F34.2.141
  61. Psychoactive Drug Screening Program (PDSP)
    https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=diphenhydramine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query
  62. European Journal of Pharmacology
    https://doi.org/10.1016%2Fs0014-2999%2897%2901393-9
  63. Sleep Medicine Reviews
    https://doi.org/10.1016%2Fj.smrv.2012.08.001
  64. J. Pharm. Pharmacol
    https://doi.org/10.1111%2Fj.2042-7158.1992.tb03235.x
  65. Bioorganic & Medicinal Chemistry
    https://doi.org/10.1016%2Fj.bmc.2006.05.077
  66. Proceedings of the National Academy of Sciences of the United States of America
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC50824
  67. Molecular Pharmacology
    https://doi.org/10.1124%2Fmol.55.6.1101
  68. Molecular Pharmacology
    https://doi.org/10.1124%2Fmol.59.3.420
  69. The Journal of Pharmacology and Experimental Therapeutics
    https://doi.org/10.1016%2FS0022-3565%2825%2911335-9
  70. Brain Research
    https://doi.org/10.1016%2FS0006-8993%2800%2902860-2
  71. FEBS Letters
    https://doi.org/10.1016%2F0014-5793%2896%2900355-9
  72. Indian Journal of Pharmacology
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195115
  73. Medscape Reference
    http://emedicine.medscape.com/article/812828-overview
  74. Psychosomatic Medicine
    https://doi.org/10.1097%2F00006842-199909000-00002
  75. Neuropeptides
    https://doi.org/10.1016%2F0143-4179%2885%2990041-1
  76. Journal of Molecular Biology
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021489
  77. Molecular Pharmacology
    https://doi.org/10.1016%2FS0026-895X%2825%2912747-8
  78. Crystal Growth & Design
    https://ui.adsabs.harvard.edu/abs/2017CrGrD..17.6030W
  79. Chromatographia
    https://doi.org/10.1365%2Fs10337-009-0977-3
  80. Journal of Chromatographic Science
    https://doi.org/10.1093%2Fchrsci%2F49.4.281
  81. DICP
    https://doi.org/10.1177%2F106002809102500204
  82. Clinical Toxicology
    https://doi.org/10.1080%2F15563650802116151
  83. PubChem
    https://pubchem.ncbi.nlm.nih.gov/compound/8980
  84. PubChem
    https://pubchem.ncbi.nlm.nih.gov/compound/174697
  85. drugs.com
    https://www.drugs.com/medical-answers/difference-between-diphenhydramine-hydrochloride-3510045/
  86. J Clin Pharmacol
    https://doi.org/10.1002%2Fj.1552-4604.1998.tb04466.x
  87. Clin Pharmacol Drug Dev
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947143
  88. Forensic Science (Handbook of Analytical Separations)
  89. Pediatric Emergency Care
    https://doi.org/10.1097%2FPEC.0b013e3181f05443
  90. The New York Times
    https://www.nytimes.com/2007/09/29/business/29rieveschl.html
  91. Drug Discovery: A History
    https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA405
  92. "UC prof, Benadryl inventor dies"
    http://www.bizjournals.com/cincinnati/stories/2007/09/24/daily52.html
  93. Chest
    http://journal.publications.chestnet.org/article.aspx?articleid=1094281
  94. Better Than Prozac
    https://archive.org/details/betterthanprozac00baro/page/39
  95. Richmond Times-Dispatch
    https://www.newspapers.com/image/829865821/
  96. Drugs.com
    https://www.drugs.com/otc/110643/childrens-benadryl-allergy.html
  97. "Is P&G Preparing to Expand ZzzQuil?"
    https://adage.com/article/cmo-strategy/p-g-preparing-expansion-zzzquil/293998
  98. Mother To Baby | Fact Sheets [Internet]
    https://www.ncbi.nlm.nih.gov/books/NBK582675/
  99. Federal Register
    https://web.archive.org/web/20081105004602/https://www.fda.gov/OHRMS/DOCKETS/98fr/120602a.htm
  100. Journal of Analytical Toxicology
    https://doi.org/10.1093%2Fjat%2F29.7.738
  101. Disposition of Toxic Drugs and Chemicals in Man
  102. "List of prohibited and controlled drugs according to chapter 96 of the laws of Zambia"
    https://web.archive.org/web/20131116010729/http://www.gctrips.org/documents/IllegaldrugsinZambia.docx
  103. Country Information > Zambia
    https://travel.state.gov/content/passports/english/country/zambia.html
  104. Articles & Interviews
    https://www.studentdoctor.net/2008/07/26/atypical-drugs-of-abuse/
  105. Neuroscience and Biobehavioral Reviews
    https://web.archive.org/web/20200802230007/https://www.queensu.ca/psychology/sites/webpublish.queensu.ca.psycwww/files/files/Faculty/Richard%20Beninger/Beninger_prp_25.pdf
  106. Journal of Child and Adolescent Psychopharmacology
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025184
  107. Journal of Clinical Psychopharmacology
    https://doi.org/10.1097%2F00004714-198802000-00003
  108. Experimental and Clinical Psychopharmacology
    https://doi.org/10.1037%2F1064-1297.4.4.421
  109. TikTok Videos Encourage Viewers to Overdose on Benadryl
    https://www.checkupnewsroom.com/tiktok-videos-encourage-viewers-to-overdose-on-benadryl/
  110. KFOR.com Oklahoma City
    https://kfor.com/news/local/dangerous-benadryl-challenge-on-tik-tok-blamed-for-the-death-of-oklahoma-teen/
  111. medpagetoday.com
    https://www.medpagetoday.com/pediatrics/generalpediatrics/88816
  112. The Independent
    https://www.independent.co.uk/news/long_reads/world/tiktok-benadryl-challenge-death-13-year-old-b2325133.html
  113. Drugs.com
    https://www.drugs.com/medical-answers/benadryl-hat-man-3573469/
  114. Rolling Stone
    https://www.rollingstone.com/culture/culture-features/hat-man-benadryl-tiktok-monster-1234620397/
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