Meclizine

{{Short description|Chemical compound}} {{Redirect2|Bonine|Dramamine II|the surname|Bonine (surname)||Dramamine (disambiguation)}} {{Use dmy dates|date=October 2022}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 402382239 | image = Meclizine.svg | image_class = skin-invert-image | width = 200 | alt =

| pronounce = | tradename = Bonine, Antivert, others | Drugs.com = {{drugs.com|monograph|meclizine-hydrochloride}} | MedlinePlus = a682548 | DailyMedID = Meclizine | pregnancy_AU =  | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = By mouth, under the tongue, in the cheek | class = | ATC_prefix = R06 | ATC_suffix = AE05 | ATC_supplemental =

| bioavailability = 22 - 32%<ref name="bioavail">{{cite journal | vauthors = Sun J, Liu J, Zhang J, Xia H |title=Meclizine-loaded nanostructured lipid carriers to manage nausea and vomiting: Oral bioavailability improvement |journal=Journal of Drug Delivery Science and Technology |date=June 2021 |volume=63 |article-number=102432 |doi=10.1016/j.jddst.2021.102432}}</ref> | protein_bound = | metabolism = Liver (CYP2D6) | metabolites = | elimination_half-life = 5-6 hours<ref name="pharmacokinetics">{{cite journal | vauthors = Wang Z, Lee B, Pearce D, Qian S, Wang Y, Zhang Q, Chow MS | title = Meclizine metabolism and pharmacokinetics: formulation on its absorption | journal = Journal of Clinical Pharmacology | volume = 52 | issue = 9 | pages = 1343–1349 | date = September 2012 | pmid = 21903894 | doi = 10.1177/0091270011414575 }}</ref> | duration_of_action = | excretion =

| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 569-65-3 | PubChem = 4034 | IUPHAR_ligand = 2757 | DrugBank_Ref = {{drugbankcite|changed|drugbank}} | DrugBank = DB00737 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 3894 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 3L5TQ84570 | KEGG = D08163 | KEGG2 = D01317 | ChEBI = | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1623 | NIAID_ChemDB = | PDB_ligand = | synonyms = Meclozine

| IUPAC_name = (''RS'')-1-[(4-chlorophenyl)(phenyl)methyl]-4-(3-methylbenzyl)piperazine | C=25 | H=27 | Cl=1 | N=2 | SMILES = Clc1ccc(cc1)C(c2ccccc2)N3CCN(CC3)Cc4cccc(c4)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C25H27ClN2/c1-20-6-5-7-21(18-20)19-27-14-16-28(17-15-27)25(22-8-3-2-4-9-22)23-10-12-24(26)13-11-23/h2-13,18,25H,14-17,19H2,1H3 | StdInChI_comment = | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = OCJYIGYOJCODJL-UHFFFAOYSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = 230 | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''Meclizine''', sold under the brand name '''Bonine''', among others, is an antihistamine used to treat motion sickness and dizziness (vertigo).<ref name=AHFS2019>{{cite web |title=Meclizine Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/meclizine-hydrochloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=22 March 2019 }}</ref> It is taken by mouth.<ref name=AHFS2019/> Effects generally begin in an hour and last for up to a day.<ref name=AHFS2019/>

Common side effects include sleepiness and dry mouth.<ref name=AHFS2019/> Serious side effects may include allergic reactions.<ref name=AHFS2019/> Use in pregnancy appears safe, but has not been well studied; use in breastfeeding is of unclear safety.<ref name=Preg2019>{{cite web |title=Meclizine Use During Pregnancy |url=https://www.drugs.com/pregnancy/meclizine.html |website=Drugs.com |access-date=3 March 2019}}</ref> It is believed to work in part by anticholinergic and antihistamine mechanisms.<ref name=AHFS2019/>

Meclizine was patented in 1951 and came into medical use in 1953.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=547 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA547 }}</ref> It is available as a generic medication and often over the counter.<ref name=AHFS2019/><ref>{{cite book | vauthors = Cappa M, Cianfarani S, Ghizzoni L, Loche S, Maghnie M |title=Advanced Therapies in Pediatric Endocrinology and Diabetology: Workshop, Rome, October 2014 |date=2015 |publisher=Karger Medical and Scientific Publishers |isbn=978-3-318-05637-2 |page=101 |url=https://books.google.com/books?id=myNRCwAAQBAJ&pg=PA101 }}</ref> In 2023, it was the 137th most commonly prescribed medication in the United States, with more than 4{{nbsp}}million prescriptions.<ref name="Top 300">{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Meclizine Drug Usage Statistics, United States, 2014 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Meclizine | access-date = 18 August 2025 }}</ref>

==Medical uses== Meclizine is used to treat symptoms of motion sickness.<ref name="Houston_2022">{{cite book | vauthors = Houston BT, Chowdhury YS | chapter = Meclizine | date = 18 July 2022 | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid = 32809480 | doi = | chapter-url = https://pubmed.ncbi.nlm.nih.gov/32809480/ }}</ref>

===Motion sickness=== Meclizine is effective in inhibiting nausea, vomiting, and dizziness caused by motion sickness.<ref>{{Cite web|url=https://www.webmd.com/drugs/2/drug-144800/motion-sickness-meclizine-oral/details|title=Drugs & Medications|website=www.webmd.com|access-date=28 December 2018}}</ref>

The drug is safe for treating nausea in pregnancy and is a first-line therapy for this use.<ref>{{cite journal|url=https://www.arznei-telegramm.de/html/2009_10/0910087_01.html|journal=Arznei-Telegramm|title=Antiemetische Therapie bei Schwangerschaftserbrechen|trans-title=Antiemetic therapy in pregnancy|year=2009|volume=40|pages=87–89|language=de}}</ref><ref>{{cite web | url = https://www.embryotox.de/meclozin.html | work = Embryotox | title = Meclozin | language = de | publisher = Bundesministerium für Gesundheit | trans-title = Federal Ministry of Health }}</ref> Meclizine may not be strong enough for especially sickening motion stimuli, and second-line defenses should be tried in those cases.<ref>{{cite web | vauthors = Lawson BD, McGee HA, Castaneda MA, Golding JF, Kass SJ, McGrath CM | title = Evaluation of several common antimotion sickness medications and recommendations concerning their potential usefulness during special operations. | publisher = Naval Aerospace Research Lab | location = Pensacola, Florida | date = 2 December 2009 | url = http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html&identifier=ADA511823 | access-date = 7 February 2016 | archive-url = https://web.archive.org/web/20160427090307/http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html&identifier=ADA511823 | archive-date = 27 April 2016 }}</ref>

===Vertigo=== Meclizine may be used to treat vertigo, such as in those with Ménière's disease.<ref>{{cite journal | vauthors = Nakashima T, Pyykkö I, Arroll MA, Casselbrant ML, Foster CA, Manzoor NF, Megerian CA, Naganawa S, Young YH | title = Meniere's disease | journal = Nature Reviews. Disease Primers | volume = 2 | article-number = 16028 | date = May 2016 | pmid = 27170253 | doi = 10.1038/nrdp.2016.28 | s2cid = 3987838 |author-link2=Ilmari Pyykkö}}</ref><ref>{{cite book | vauthors = | chapter = Meclizine | title = LiverTox: Clinical and Research Information on Drug-Induced Liver Injury | date = January 2017 | pmid = 31643231 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK547895/ | location = Bethesda (MD) | publisher = National Institute of Diabetes and Digestive and Kidney Diseases }}</ref>

==Side effects== Some common side effects such as drowsiness, dry mouth, and tiredness may occur. Meclizine has been shown to have fewer dry mouth side effects than the traditional treatment for motion sickness, transdermal scopolamine.<ref name="pmid6734040">{{cite journal | vauthors = Dahl E, Offer-Ohlsen D, Lillevold PE, Sandvik L | title = Transdermal scopolamine, oral meclizine, and placebo in motion sickness | journal = Clinical Pharmacology and Therapeutics | volume = 36 | issue = 1 | pages = 116–120 | date = July 1984 | pmid = 6734040 | doi = 10.1038/clpt.1984.148 | s2cid = 40691502 }}</ref> A very serious allergic reaction to this drug is unlikely, but immediate medical attention should be sought if it occurs. Symptoms of a serious allergic reaction may include rash, itching, swelling, severe dizziness, and trouble breathing.<ref>{{cite web | url = https://www.medicinenet.com/meclizine_cyclizine-oral/article.htm | title = Meclizine - oral, Antivert, D-vert, Dramamine II | access-date = 7 November 2010 | work = MedicineNet }}</ref>

== Pharmacology == === Pharmacodynamics === Meclizine is an antagonist at H1 receptors (''K''i = 250 nM).<ref>{{cite journal | vauthors = Tran VT, Chang RS, Snyder SH | title = Histamine H1 receptors identified in mammalian brain membranes with [3H]mepyramine | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 75 | issue = 12 | pages = 6290–6294 | date = December 1978 | pmid = 282646 | pmc = 393167 | doi = 10.1073/pnas.75.12.6290 | doi-access = free }}</ref> It possesses anticholinergic, central nervous system depressant, and local anesthetic effects. Its antiemetic and antivertigo effects are not fully understood, but its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone.<ref name="Houston_2022" /> The drug has been shown to reduce the magnitude of the vestibulo-ocular reflex in healthy volunteers.<ref name="weerts">{{cite journal | vauthors = Weerts AP, De Meyer G, Pauwels G, Vanspauwen R, Dornhoffer JL, Van de Heyning PH, Wuyts FL | title = Pharmaceutical countermeasures have opposite effects on the utricles and semicircular canals in man | journal = Audiology & Neuro-Otology | volume = 17 | issue = 4 | pages = 235–242 | date = 2012 | pmid = 22517315 | doi = 10.1159/000337273 }}</ref> At the same time the drug was found to have only a small (and statistically insignificant) effect on the motion sensitivity of the utricles.<ref name="weerts"/> Much as motion sickness arises from a discrepancy between multiple senses, meclizine most likely affects a wide array of sensory mechanisms related to self-motion while leaving the core vestibular response intact.<ref>{{cite journal | vauthors = Wibble T, Engström J, Verrecchia L, Pansell T | title = The effects of meclizine on motion sickness revisited | journal = British Journal of Clinical Pharmacology | volume = 86 | issue = 8 | pages = 1510–1518 | date = August 2020 | pmid = 32077140 | pmc = 7373708 | doi = 10.1111/bcp.14257 | doi-access = free }}</ref>

Meclizine also has been reported to be a weak dopamine antagonist at D1-like and D2-like receptors{{citation needed|date=September 2015}} but it does not cause catalepsy in mice, perhaps because of its anticholinergic activity.<ref name=Haraguchi_1997>{{cite journal | vauthors = Haraguchi K, Ito K, Kotaki H, Sawada Y, Iga T | title = Prediction of drug-induced catalepsy based on dopamine D1, D2, and muscarinic acetylcholine receptor occupancies | journal = Drug Metabolism and Disposition | volume = 25 | issue = 6 | pages = 675–684 | date = June 1997 | pmid = 9193868 | url = http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9193868 | access-date = 12 June 2014 | archive-url = https://web.archive.org/web/20210828114146/https://dmd.aspetjournals.org/content/25/6/675.long | archive-date = 28 August 2021 }} "Catalepsy was assessed by the bar method: the front paws were gently placed on a horizontal metal bar with 2 mm diameter suspended 4 cm above, and the length of time the mouse maintains this abnormal posture was measured."</ref> The drug does not affect dopamine or serotonin reuptake.<ref>{{cite journal | vauthors = Oishi R, Shishido S, Yamori M, Saeki K | title = Comparison of the effects of eleven histamine H1-receptor antagonists on monoamine turnover in the mouse brain | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 349 | issue = 2 | pages = 140–144 | date = February 1994 | pmid = 7513381 | doi = 10.1007/BF00169830 }}</ref>

=== Pharmacokinetics === Meclizine reaches peak plasma concentration in about 1.5 hours and has an elimination half-life of 5–6 hours.<ref name="pharmacokinetics"/> Despite its relatively short half-life, the drug is reported to remain effective for motion sickness for 12 – 24 hours.<ref>{{cite web |title=ANTIVERT FDA Drug Facts |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/010721s058lbl.pdf |publisher=FDA |access-date=18 June 2024}}</ref> Meclizine has low bioavailability (22–32%) and a delayed onset to action in part due to its poor solubility in water (0.1 mg/ml) and gastrointestinal fluid.<ref name="bioavail"/> In children it has been found that taking meclizine with food increases its bioavailability slightly.<ref name="kids">{{cite journal | vauthors = Kitoh H, Matsushita M, Mishima K, Nagata T, Kamiya Y, Ueda K, Kuwatsuka Y, Morikawa H, Nakai Y, Ishiguro N | title = Pharmacokinetics and safety after once and twice a day doses of meclizine hydrochloride administered to children with achondroplasia | journal = PLOS ONE | volume = 15 | issue = 4 | article-number = e0229639 | date = 13 April 2020 | pmid = 32282831 | pmc = 7153885 | doi = 10.1371/journal.pone.0229639 | doi-access = free | bibcode = 2020PLoSO..1529639K }}</ref> It is metabolized in the liver by the CYP2D6 enzyme.<ref name="pharmacokinetics"/> Ten metabolites have been identified.<ref>{{cite journal | vauthors = Goenechea VS, Rücker G, Brzezinka H, Hoffmann G, Neugebauer M, Glanzmann G | title = [Biotransformation of meclozine in the human body] | journal = Journal of Clinical Chemistry and Clinical Biochemistry | volume = 26 | issue = 2 | pages = 105–115 | date = February 1988 | pmid = 3367105 }}</ref> In rats, the main metabolite is norchlorcyclizine, which distributes extensively through body tissue.<ref>{{cite journal | vauthors = Narrod SA, Wilk AL, King CT | title = Metabolism of Meclizine in the Rat | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 147 | pages = 380–384 | date = March 1965 | issue = 3 | doi = 10.1016/S0022-3565(25)26997-X | pmid = 14269614 }}</ref>

==Chemistry== Meclizine is a first-generation antihistamine (nonselective H1 antagonist) of the piperazine class. It is structurally and pharmacologically similar to buclizine, cyclizine, and hydroxyzine.

===Synthesis=== (4-Chlorophenyl)-phenylmethanol is halogenated with thionyl chloride before adding acetylpiperazine. The acetyl group is cleaved with diluted sulfuric acid. An N-alkylation of the piperazine ring with 3-methylbenzylchloride completes the synthesis.<ref>{{cite book| vauthors = Fuhrkop JH, Li G | title = Organic Synthesis. Concepts and Methods |publisher=Wiley |year=2003 |page=237 |isbn=978-3-527-30272-7 }}</ref>

762px|class=skin-invert-image

Alternatively, the last step can be replaced by a reductive N-alkylation with 3-methylbenzaldehyde. The reductive agent is hydrogen, and Raney nickel is used as a catalyst.<ref>{{cite patent | country = US | number = 2709169 | inventor = Morren H | assign1 = Union Chimique Belge Société Anonyme | gdate = 24 May 1955 | url = https://patents.google.com/patent/US2709169?oq=US2709169 }}</ref><ref name="Kleemann">{{cite book| vauthors = Kleemann A, Engel J, Kutscher B, Reichert D |title= Pharmaceutical Substances. Synthesis, Patents, Applications |edition=4th |publisher=Thieme |year=2001 |isbn=3-13-115134-X }}</ref>

586px|class=skin-invert-image

Meclizine is obtained and used as a racemate, a 1:1 mixture of the two stereoisomers. Drug forms contain the racemic dihydrochloride.{{citation needed|date=August 2020}}

== Society and culture == === Brand names === Meclizine is an international nonproprietary name.<ref>{{cite web | url = http://whqlibdoc.who.int/hq/1997/WHO_PHARM_S_NOM_1570.pdf | title = Guidelines on the Use of INNs for Pharmaceutical Substances | date = 1997 | access-date = 1 November 2013 | work = WHO }}</ref>

It is sold under the brand names Bonine, Bonamine, Antivert, Postafen, Sea Legs, and Dramamine II (Less Drowsy Formulation). Emesafene is a combination of meclizine (1/3) and pyridoxine (2/3). In Canada, Antivert Tab was a combination of meclizine and nicotinic acid.<ref>{{cite web | work = DrugBank | url = http://www.drugbank.ca/drugs/DB00737 | title = Drug card for Meclizine | vauthors = Wishard D | publisher = University of Alberta | location = Canada | access-date = 7 November 2010 }}</ref>

== References == {{reflist}}

{{Navboxes | title = Medical uses | titlestyle = background:#ccccff | list1 = {{Antiemetics}} {{Antihistamines}} {{Motion sickness}} {{Hallucinogens}} }} {{Navboxes | title = Pharmacodynamics | titlestyle = background:#ccccff | list1 = {{Histamine receptor modulators}} {{Ion channel modulators}} {{Muscarinic acetylcholine receptor modulators}} {{Xenobiotic-sensing receptor modulators}} }} {{Portal bar | Medicine}} {{Authority control}}

Category:Antiemetics Category:Benzylpiperazines Category:Chlorcyclizines Category:Motion sickness Category:Pregnane X receptor agonists Category:Wikipedia medicine articles ready to translate Category:3-Tolyl compounds Category:Over-the-counter drugs in the United States