View source for Dimenhydrinate

{{Short description|Anti-emetic and antihistamine medication}}
{{distinguish|diphenhydramine}}
{{redirect|Dramamine}}
{{Use dmy dates|date=February 2022}}
{{Infobox drug
| Verifiedfields     = changed
| Watchedfields      = changed
| verifiedrevid      = 459441657
| type               = combo
| image              = Dimenhydrinate.svg
| image_class        = skin-invert-image
| width              = 160
| alt                = 
| caption            =

<!-- Combo data -->
| component1         = Diphenhydramine
| class1             = [[Antihistamine]], [[sedative]]
| component2         = 8-chlorotheophylline
| class2             = [[Stimulant]]
| tradename          = Dramamine, Draminate, Gravol, others
| Drugs.com          = {{drugs.com|monograph|dimenhydrinate}}
| MedlinePlus        = a607046
| DailyMedID         = Dimenhydrinate
| pregnancy_AU       = A
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [[By mouth]], [[Rectal administration|rectal]], {{linktext|intravascular}}, [[intramuscular]]
| ATCvet             = 
| ATC_prefix         = R06
| ATC_suffix         = AA11
| ATC_supplemental   = combinations {{ATC|R06|AA61}}

<!-- Pharmacokinetic data -->
| bioavailability    =  
| protein_bound      =  
| metabolism         = [[Liver]]
| elimination_half-life = 5.5 hours<ref name="oral_sublingual2328304">{{cite journal | vauthors = Scavone JM, Luna BG, Harmatz JS, von Moltke L, Greenblatt DJ | title = Diphenhydramine kinetics following intravenous, oral, and sublingual dimenhydrinate administration | journal = Biopharmaceutics & Drug Disposition | volume = 11 | issue = 3 | pages = 185–189 | date = April 1990 | pmid = 2328304 | doi = 10.1002/bdd.2510110302 }}</ref> (diphenhydramine component)
| excretion          = 
 
<!-- Legal status -->
| legal_AU           = S2
| legal_AU_comment   = 
| legal_BR           = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment   = 
| legal_CA           = [[Over-the-counter drug|OTC]]
| legal_CA_comment   = 
| legal_DE           = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment   = 
| legal_NZ           = <!-- Class A, B, C -->
| legal_NZ_comment   = 
| legal_UK           = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment   = 
| legal_US           = OTC
| legal_US_comment   = 
| legal_EU           = 
| legal_EU_comment   = 
| legal_UN           = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment   = 
| legal_status       = <!-- For countries not listed above -->

<!-- Identifiers -->
| CAS_number_Ref     = {{cascite|correct|??}}
| CAS_number         = 523-87-5
| CAS_supplemental   = 
| PubChem            = 10660
| IUPHAR_ligand      = 
| DrugBank_Ref       = {{drugbankcite|correct|drugbank}}
| DrugBank           = DB00985
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 10210
| UNII_Ref           = {{fdacite|correct|FDA}}
| UNII               = JB937PER5C
| KEGG_Ref           = {{keggcite|correct|kegg}}
| KEGG               = D00520
| ChEBI              = 94848
| ChEMBL_Ref         = {{ebicite|changed|EBI}}
| ChEMBL             = 1200406
| NIAID_ChemDB       = 
| PDB_ligand         = 
| synonyms           = Diphenhydramine/8-chlorotheophylline salt
}}

'''Dimenhydrinate''', also known as '''diphenhydramine/8-chlorotheophylline salt''' and sold under the brand names '''Dramamine''' and '''Gravol''', among others, is an [[over-the-counter medication]] used to treat [[motion sickness]] and [[nausea]]. Dimenhydrinate is a [[Theophylline|theoclate]] salt composed of [[diphenhydramine]] and [[8-chlorotheophylline]] (a [[theophylline]] relative) in a 1:1 ratio.<ref name = "Hemmings_2019">{{Cite book |chapter-url=https://www.sciencedirect.com/science/article/pii/B978032348110600034X |title=Pharmacology and Physiology for Anesthesia | edition = Second |chapter=34 - Pharmacology of Postoperative Nausea and Vomiting |publisher=[[Elsevier Inc.]] |year=2019 |isbn=978-0-323-48110-6 | veditors = Hemmings Jr HC, Talmage ED |pages=671–692 |doi=10.1016/B978-0-323-48110-6.00034-X |s2cid=81387334 | vauthors = Zabirowicz ES, Gan TJ }}</ref>

Dimenhydrinate was introduced to the market by [[G.D. Searle]] in 1949.<ref name="Newman 2012">{{cite web | vauthors = Newman A |title=New Dramamine Ads Take Aim at Summer Vacationers |website=The New York Times |date=21 June 2012 |url=https://www.nytimes.com/2012/06/21/business/media/new-dramamine-ads-take-aim-at-summer-vacationers.html |access-date=26 June 2023}}</ref><ref name="Grauer 2019">{{cite web | vauthors = Grauer N |title=Hopkins History Moments: Neil A. Grauer explains how Hopkins expertise helped prevent seasickness |website=Johns Hopkins Medicine |date=12 February 2019 |url=https://www.hopkinsmedicine.org/news/articles/hopkins-history-moments-3 |access-date=27 June 2023}}</ref>

== Medical uses ==
[[File:Dimenhydrinate .jpg|thumb|Pills sold in Phonm Penh over the counter]]
Dimenhydrinate is an [[Over-the-counter drug|over-the-counter]] (OTC) first-generation [[antihistamine]] indicated for the prevention and relief of nausea and vomiting from a number of causes, including motion-sickness and post-operative nausea.<ref name = "Hemmings_2019" />

== Side effects ==
Common side effects of dimenhydrinate may include [[drowsiness]], [[dry mouth]], nose, or throat, [[constipation]], and [[blurred vision]]. Some individuals, particularly children, may experience feelings of [[Psychomotor agitation|restlessness]] or excitement. In certain cases, more severe symptoms may arise, such as [[delirium]], weakness, and a tendency to be easily [[startle]]d. [[Hallucination]]s, [[psychosis]], and an unusual sensitivity to sudden sounds have also been reported.<ref>{{Cite web |title= Dimenhydrinate |url= https://www.drugs.com/mtm/dimenhydrinate.html#side-effects |url-status=live |website=Drugs.com |archive-url= https://web.archive.org/web/20040528004841/http://www.drugs.com:80/MTM/dimenhydrinate.html |archive-date=28 May 2004|access-date=28 May 2004 }}</ref><ref>{{cite journal | vauthors = Fabiano N, Dholakia S, Walker LA, Smith AL | title = Chronic high-dose dimenhydrinate use contributing to early multifactorial cognitive impairment | journal = BMJ Case Reports | volume = 17 | issue = 3 | article-number = e258493 | date = March 2024 | pmid = 38453220 | pmc = 10921430 | doi = 10.1136/bcr-2023-258493 | pmc-embargo-date = March 7, 2026 }}</ref><ref>{{cite web |url=https://www.webmd.com/drugs/2/drug-8645/dimenhydrinate-oral/details |title=Dimenhydrinate Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD }}</ref> Continuous and/or cumulative use of [[anticholinergic]] medications, including first-generation antihistamines, is associated with higher risk of cognitive decline and dementia in older people. However, in younger people this is not relevant.<ref>{{cite journal | vauthors = Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB | display-authors = 6 | title = Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study | journal = JAMA Internal Medicine | volume = 175 | issue = 3 | pages = 401–407 | date = March 2015 | pmid = 25621434 | pmc = 4358759 | doi = 10.1001/jamainternmed.2014.7663 | author5-link = Rebecca Hubbard }}</ref><ref>{{cite journal | vauthors = Carrière I, Fourrier-Reglat A, Dartigues JF, Rouaud O, Pasquier F, Ritchie K, Ancelin ML | title = Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study | journal = Archives of Internal Medicine | volume = 169 | issue = 14 | pages = 1317–1324 | date = July 2009 | pmid = 19636034 | pmc = 2933398 | doi = 10.1001/archinternmed.2009.229 }}</ref>

== Pharmacology ==
===Pharmacodynamics===
[[Diphenhydramine]] is the primary constituent of dimen{{shy}}hydrinate and dictates the primary effect. The main differences relative to pure diphen{{shy}}hydramine are a lower [[potency (pharmacology)|potency]] due to being combined with 8-chloro{{shy}}theo{{shy}}phylline (by weight, dimen{{shy}}hydrinate is between 53% and 55.5% diphen{{shy}}hydramine)<ref>{{cite web|title=Dimenhydrinate injection, solution|url=https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=bc71539e-1a33-4709-8a24-c2894e8dbc1c|url-status=live|archive-url=https://web.archive.org/web/20141013094705/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bc71539e-1a33-4709-8a24-c2894e8dbc1c|archive-date=13 October 2014|access-date=19 July 2014|website=Daily Med|publisher=U.S. National Library of Medicine}}<nowiki>}}</nowiki></ref> and the fact that the stimulant properties of 8-chloro{{shy}}theo{{shy}}phylline help reduce the side effect of drowsiness brought on by diphen{{shy}}hydramine. Diphen{{shy}}hydramine is itself an [[Histamine H1 receptor|H<sub>1</sub> receptor]] [[Receptor antagonist|antagonist]] that demonstrates [[anticholinergic]] activity.<ref name="review">{{cite journal | vauthors = ((Canadian Agency for Drugs and Technologies in Health)) | title = Abuse and Misuse Potential of Dimenhydrinate: A Review of the Clinical Evidence [Internet] | journal = CADTH Rapid Response Reports. | date = 2015 | pmid = 26985532 }}</ref>

=== Pharmacokinetics ===
The diphenhydramine component requires about 2{{spaces}}hours to reach peak concentration after either oral or sublingual administration of dimen{{shy}}hydrinate, and has a half-life of {{nowrap|5{{hsp}}{{ndash}}{{hsp}}}}6{{spaces}}hours in healthy adults.<ref name="oral_sublingual2328304"/>

== Recreational use ==
Dimenhydrinate is recreationally used as a [[deliriant]].<ref>{{Cite web|url=http://www.narconon.org/drug-abuse/prescription/motion-sickness-pills.html|title=The Health Risks of Abusing Motion sickness pills|website=Narconon International|access-date=13 September 2016}}</ref><ref name=":0">{{cite journal | vauthors = Lessenger JE, Feinberg SD | title = Abuse of prescription and over-the-counter medications | journal = Journal of the American Board of Family Medicine | volume = 21 | issue = 1 | pages = 45–54 | date = 2008 | pmid = 18178702 | doi = 10.3122/jabfm.2008.01.070071 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Gardner DM, Kutcher S | title = Dimenhydrinate abuse among adolescents | journal = Canadian Journal of Psychiatry | volume = 38 | issue = 2 | pages = 113–116 | date = March 1993 | pmid = 8467436 | doi = 10.1177/070674379303800208 | s2cid = 30190588 }}</ref> Slang terms for Dramamine used this way include "drama", "dime", "dime tabs", "D-Q", "substance D", "d-house", and "drams".<ref>{{Cite web|url=http://www.brighthub.com/science/medical/articles/51711.aspx|title=The Dangers of Dimenhydrinate Abuse|website=Bright Hub|access-date=13 September 2016|date=6 October 2009| vauthors = Trix V }}</ref> Abusing Dramamine is sometimes referred to as Dramatizing or "going a dime a dozen", a reference to the number of Dramamine tablets generally necessary for a recreational dose.
<ref>
{{cite web
   | last = Harrison
   | first = Karl
   | title = 3DChem.com - Chemistry, Structures & 3D Molecules
   | url = https://www.3dchem.com/Dimenhydrinate.asp
   | date = 2010-03-01
		| access-date = 2025-08-11
}}</ref>

Many users report a side-effect profile consistent with [[tropane alkaloid]] (e.g., [[atropine]]) poisoning as both show antagonism of [[muscarinic acetylcholine receptor]]s in both the [[central nervous system | central]] and [[autonomic nervous system]], which inhibits various signal transduction pathways.<ref name=":0" />

Other CNS effects occur within the [[limbic system]] and [[hippocampus]], causing [[confusion]] and temporary [[amnesia]] due to decreased [[acetylcholine]] signaling. [[Toxicity]] manifests in the autonomic nervous system, primarily at the [[neuromuscular junction]], resulting in [[ataxia]] and [[extrapyramidal side effects]] and the feeling of heaviness in the legs, and at sympathetic post-ganglionic junctions, causing urinary retention, pupil dilation, [[tachycardia]], irregular urination, and dry red skin caused by decreased [[exocrine gland]] secretions, and mucous membranes. Considerable overdosage can lead to [[myocardial infarction]] (heart attack), serious [[Heart arrhythmia|ventricular arrhythmias]], coma, and death.<ref>{{Cite web|url=http://www.muirwoodteen.com/over-the-counter-drug-abuse/motion-sickness-pills/|title=Are Teens Abusing Motion Sickness Pills? - Muir Wood Adolescent and Family Services|language=en-US|access-date=13 September 2016|archive-url=https://web.archive.org/web/20160918160015/http://www.muirwoodteen.com/over-the-counter-drug-abuse/motion-sickness-pills/|archive-date=18 September 2016}}</ref> Such a side-effect profile is thought to give [[ethanolamine]]-class antihistamines a relatively low abuse liability.{{citation needed|date=May 2022}} An antidote that can be used for dimenhydrinate poisoning is [[physostigmine]].<ref>{{cite journal | vauthors = Scharman EJ, Erdman AR, Wax PM, Chyka PA, Caravati EM, Nelson LS, Manoguerra AS, Christianson G, Olson KR, Woolf AD, Keyes DC, Booze LL, Troutman WG | display-authors = 6 | title = Diphenhydramine and dimenhydrinate poisoning: an evidence-based consensus guideline for out-of-hospital management | journal = Clinical Toxicology | volume = 44 | issue = 3 | pages = 205–223 | date = 19 January 2006 | pmid = 16749537 | doi = 10.1080/15563650600585920 | s2cid = 702353 }}</ref>

== History ==
Dimenhydrinate (originally known as Compound 1694) was being tested as a potential treatment for [[hay fever]] and [[hives]] at [[Johns Hopkins Hospital]] in 1947 by allergists Dr. Leslie Gay and Dr. Paul Carliner. Among those who received the drug was a pregnant woman who had suffered from motion sickness her entire life. She remained symptom-free if she took dimenhydrinate a few minutes before boarding a trolley, whereas the placebo was ineffective. To confirm these findings, the following year, G.D. Searle & Co. conducted a trial in which dimenhydrinate or placebo was given to U.S. troops crossing the Atlantic during "a rough passage" in a converted freight ship, the ''[[USS General C. C. Ballou|General Ballou]]'', for ten days as a rescue therapy for [[sea sickness]]. The findings were positive, as were the findings of a second trial of mostly women on the ship's return voyage. Gay and Carliner announced their discovery at a meeting of the Johns Hopkins Medical Society on February 14, 1949, as well as in the ''Bulletin of The Johns Hopkins Hospital''. The ''[[New York Times]]'', the ''[[Baltimore Sun]]'', and other national newspapers covered the discovery, and Dramamine was made available in drugstores later that year.<ref name="Newman 2012"/><ref name="Grauer 2019"/><ref name="pmid30233361">{{cite journal |vauthors=Sanger GJ, Andrews P |title=A History of Drug Discovery for Treatment of Nausea and Vomiting and the Implications for Future Research |journal=Frontiers in Pharmacology |volume=9 |issue= |page=913 |date=2018 |pmid=30233361 |pmc=6131675 |doi=10.3389/fphar.2018.00913 |doi-access=free }}</ref>

== Brand names ==
Dimenhydrinate is marketed under many brand names: 
{| class="wikitable"
|+
!Brand name
!Countries
|-
|Anautin
|Ecuador
|-
|Antimo
|Indonesia
|-
|Aviomarin
|Poland,<ref>{{Cite web |title=Aviomarin, 50 mg, tabletki, 5 szt |url=https://www.doz.pl/apteka/p5336-Aviomarin_50_mg_tabletki_5_szt |access-date=2025-03-01 |website=doz.pl |language=pl}}</ref> Slovakia
|-
|Biodramina
|Spain
|-
|Cinfamar
|Spain, Peru, Taiwan<ref>{{Cite web |date=2024-06-22 |title=Cinfamar: Uses, Dosage, Side Effects, Food Interaction & FAQ |url=https://www.medicinesfaq.com/brand/cinfamar |access-date=2025-03-01 |website=MedicinesFAQ |language=en}}</ref>
|-
|Daedalon
|Hungary
|-
|Dimigal
|Serbia
|-
|Dramamine
|U.S, Mexico, Turkey, Thailand
|-
|Dramin
|Brazil
|-
|Dramina
|Russia, Croatia
|-
|Driminate
|Ukraine
|-
|Enjomin
|Portugal
|-
|Gravamin
|Iceland
|-
|Gravicoll
|Peru
|-
|Gravinate
|Pakistan<ref>{{cite web |title=Gravinate [Dimenhydrinate] |url=http://www.searlecompany.com/gravinate.html |archive-url=https://web.archive.org/web/20130505060333/http://www.searlecompany.com/gravinate.html |archive-date=5 May 2013 |publisher=The Searle Company |location=Karachi Pakistan}}</ref>
|-
|Gravol
|Canada, Costa Rica, India
|-
|Mareol
|Colombia
|-
|Travacalm
|Australia
|-
|Travamin
|Israel
|-
|Valontan
|Italy
|-
|Vertirosan
|Austria
|-
|Viabom
|Portugal
|-
|Vomex
|South Africa, Germany
|-
|Vomidrine
|Portugal
|-
|Xamamina
|Italy
|-
|}

== Popular culture ==
[[Modest Mouse]] produced a song titled "Dramamine" on their 1996 debut album ''[[This Is a Long Drive for Someone with Nothing to Think About]]''. The song uses side effects of the drug as a metaphor for the deteriorating state of a personal relationship.<ref>{{cite web | title = Modest Mouse: 'This is a long drive...' | url = https://shop.glacialpace.com/collections/music/products/this-is-a-long-drive-for-someone-with-nothing-to-think-about | publisher = Glacial Pace Recordings | location = Portland | access-date = 26 March 2019 | archive-date = 27 March 2019 | archive-url = https://web.archive.org/web/20190327091622/https://shop.glacialpace.com/collections/music/products/this-is-a-long-drive-for-someone-with-nothing-to-think-about }}</ref>

"The Ending of Dramamine" is the opening track of the album ''[[How to Leave Town]]'' by [[Car Seat Headrest]].

== References ==
{{reflist}}

== External links ==
* {{Commons category-inline}}

{{Antiemetics}}
{{Antivertigo preparations}}
{{Hypnotics}}
{{Motion sickness}}
{{Acetylcholine receptor modulators}}
{{Histamine receptor modulators}}
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[[Category:Antiemetics]]
[[Category:Combination drugs]]
[[Category:Deliriants]]
[[Category:H1 receptor antagonists]]
[[Category:M1 receptor antagonists]]
[[Category:M2 receptor antagonists]]
[[Category:M4 receptor antagonists]]
[[Category:M5 receptor antagonists]]
[[Category:Motion sickness]]
[[Category:Dimethylamino compounds]]
[[Category:Over-the-counter drugs in the United States]]
[[Category:Hallucinogens]]