Meclizine: Difference between revisions

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			{{Short description\|Chemical compound}}
	{{drugbox
			{{Redirect2\|Bonine\|Dramamine II\|the surname\|Bonine (surname)\|\|Dramamine (disambiguation)}}
	\| verifiedrevid = 395509487
			{{Use dmy dates\|date=October 2022}}
	\| IUPAC_name = (''R/S'')-1--4-(3-methylbenzyl)piperazine
			{{cs1 config \|name-list-style=vanc \|display-authors=6}}
			{{Infobox drug
			\| Verifiedfields = changed
			\| Watchedfields = changed
			\| verifiedrevid = 402382239
	\| image = Meclizine.svg		\| image = Meclizine.svg
	\| width = ~~200px~~		\| width = 200
			\| alt =
	\| CASNo_Ref = {{cascite\|correct\|CAS}}

			<!-- Clinical data -->
			\| pronounce =
			\| tradename = Bonine, Antivert, others
			\| Drugs.com = {{drugs.com\|monograph\|meclizine-hydrochloride}}
			\| MedlinePlus = a682548
			\| DailyMedID = Meclizine
			\| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
			\| pregnancy_AU_comment =
			\| pregnancy_category =
			\| routes_of_administration = ], ], ]
			\| class =
			\| ATC_prefix = R06
			\| ATC_suffix = AE05
			\| ATC_supplemental =

			<!-- Legal status -->
			\| legal_AU = S4
			\| 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 = 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 -->

			<!-- Pharmacokinetic data -->
			\| 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 \|pages=102432 \|doi=10.1016/j.jddst.2021.102432}}</ref>
			\| protein_bound =
			\| metabolism = ] (])
			\| 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 =

			<!-- Identifiers -->
			\| 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_Ref = {{fdacite\|correct\|FDA}}
	\| UNII = 3L5TQ84570		\| UNII = 3L5TQ84570
			\| KEGG = D08163
	\| InChI = 1/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
			\| KEGG2 = D01317
	\| InChIKey = OCJYIGYOJCODJL-UHFFFAOYAY
			\| ChEBI =
			\| ChEMBL_Ref = {{ebicite\|changed\|EBI}}
			\| ChEMBL = 1623
			\| NIAID_ChemDB =
			\| PDB_ligand =
			\| synonyms = Meclozine

			<!-- Chemical and physical data -->
			\| IUPAC_name = (''RS'')-1--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 = 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		\| StdInChIKey = OCJYIGYOJCODJL-UHFFFAOYSA-N
			\| density =
	\| CAS_number = 569-65-3
			\| density_notes =
	\| ChemSpiderID = 3894
			\| melting_point =
	\| ATC_prefix = A04
	\| ~~ATC_suffix~~ = ~~AB04~~		\| melting_high =
			\| melting_notes =
	\| ATC_supplemental = {{ATC\|R06\|AE05}}
	\| PubChem = 4034
	\| DrugBank = APRD00354
	\| smiles = Clc1ccc(cc1)C(c2ccccc2)N3CCN(CC3)Cc4cccc(c4)C
	\| C=25 \| H=27 \| Cl=1 \| N=2
	\| molecular_weight = 390.948 g/mol
	\| boiling_point = 230		\| boiling_point = 230
	\| ~~bioavailability~~ =		\| boiling_notes =
	\| ~~protein_bound~~ =		\| solubility =
			\| sol_units =
	\| metabolism = hepatic
			\| specific_rotation =
	\| elimination_half-life = 6 hours
	\| pregnancy_US= B
	\| legal_status = ] (]); ] (])
	\| routes_of_administration = Oral, Sublingual/Buccal
	}}		}}
	'''Meclizine''' is an ] considered to be an ]. It is sold under the brand names of '''Bonine''', '''Bonamine''', '''Antivert''', '''Postafen''', '''Sea Legs''', and '''Dramamine (Less Drowsy Formulation)'''. '''Emesafene''' is a combination of meclizine (1/3) and ] (2/3). In Canada, Antivert Tab (which is no longer available) was a combination of meclizine and ].<ref>DrugBank. David Wishard: University of Alberta, Canada. Accessed November 7, 2010.</ref>

			<!-- Definition and medical uses -->

			'''Meclizine''', sold under the brand name '''Bonine''', among others, is an ] used to treat ] and dizziness (]).<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/>

			<!-- Side effects and mechanisms -->
	==Classification==
			Common side effects include sleepiness and dry mouth.<ref name=AHFS2019/> Serious side effects may include ].<ref name=AHFS2019/> Use in ] appears safe, but has not been well studied; use in ] 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 ] and ] mechanisms.<ref name=AHFS2019/>
	Meclizine is a first-generation antihistamine of the ] class. Meclizine is structurally and pharmacologically similar to buclizine, cyclizine, and hydroxyzine. It is used as an antivertigo/antiemetic agent, specifically, in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. <ref>Clinical Pharmacology. , revised November 20, 2009, accessed November 7, 2010.</ref>

			<!-- Society and culture -->
	==Mechanism of Action==
			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=9783527607495 \|page=547 \|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA547 }}</ref> It is available as a ] and often ].<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=9783318056372 \|page=101 \|url=https://books.google.com/books?id=myNRCwAAQBAJ&pg=PA101 }}</ref> In 2022, it was the 129th most commonly prescribed medication in the United States, with more than 4{{nbsp}}million prescriptions.<ref>{{cite web \| title=The Top 300 of 2022 \| url=https://clincalc.com/DrugStats/Top300Drugs.aspx \| website=ClinCalc \| access-date=30 August 2024 \| archive-date=30 August 2024 \| archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx \| url-status=live }}</ref><ref>{{cite web \| title = Meclizine Drug Usage Statistics, United States, 2013 - 2022 \| website = ClinCalc \| url = https://clincalc.com/DrugStats/Drugs/Meclizine \| access-date = 30 August 2024 }}</ref>
	Meclizine is an antagonist at H1-receptors. It possesses ], central nervous system depressant, and local anesthetic effects. Its ] and antivertigo effects are not fully understood, but its central ] properties are partially responsible. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary ]. <ref>Clinical Pharmacology. , revised November 20, 2009, accessed November 7, 2010.</ref>

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

	Meclizine is FDA approved to treat symptoms of ] and for management of ] that stems from diseases affecting the ]. Meclizine's safety and efficacy in children younger than 12 years old has not been established, therefore use in this population is not recommended. Also, meclizine should be taken with caution in the elderly (greater than 65 years old) because of increased risk of confusion and amnesia. <ref>MICROMEDEX 2.0. . Accessed November 7, 2010.</ref>

	===Motion sickness===		===Motion sickness===
	Meclizine is effective in inhibiting ~~the symptoms of ], such as~~ nausea, vomiting, and dizziness. ~~The~~ ~~recommended~~ ~~dose~~ ~~is 25-50 mg orally, taken 1 hour before travel. The dose may be repeated every 24 hours as needed~~.<ref>~~Clinical~~ ~~Pharmacology. ,~~ ~~revised~~ ~~November 20, 2009, accessed November 7, 2010.~~</ref>		Meclizine is effective in inhibiting nausea, vomiting, and dizziness caused by ].<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 ] and is a first-line therapy for this use.<ref>{{cite journal\|url=http://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 = http://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 \| url-status = dead }}</ref>

	===Vertigo===		===Vertigo===
			Meclizine may be used to treat ], such as in those with ].<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 \| pages = 16028 \| date = May 2016 \| pmid = 27170253 \| doi = 10.1038/nrdp.2016.28 \| s2cid = 3987838 }}</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>
	Meclizine may be effective in relieving ] experienced as a result of ]s or other conditions. The recommended dose is 25-100 mg per day orally, separated into divided doses. <ref>Clinical Pharmacology. , revised November 20, 2009, accessed November 7, 2010.</ref>

	==Side ~~Effects~~==		==Side effects==
	Some common side effects such as drowsiness, dry mouth, and tiredness may occur. Meclizine has been shown to have ~~less~~ dry mouth side effects than the traditional treatment for motion sickness, transdermal ]<ref>Dahl E, Offer-Ohlsen D, Lillevold PE, Sandvik L. Transdermal scopolamine, oral meclizine, and placebo in motion sickness. Clinical Pharmacology ~~And~~ Therapeutics ~~1984~~ ~~Jul;~~ ~~Vol.~~ 36 (1), ~~pp.~~ ~~116-20.~~ ~~Available~~ ~~from:~~ ~~MEDLINE:~~ ~~Ipswich,~~ ~~MA.~~ ~~PMID~~ 6734040</ref>. A very serious allergic reaction to this drug is unlikely, but ~~seek~~ immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling, severe dizziness, and~~/or~~ trouble breathing. <ref> ~~MedicineNet.com:~~ We ~~Bring~~ ~~Doctors'~~ ~~Knowledge to You. MedicineNet Inc, San Clemente, CA. .~~ ~~Accessed~~ ~~November~~ 7, 2010.</ref>		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 ].<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 = http://www.medicinenet.com/meclizine_cyclizine-oral/article.htm \| title = Meclizine - oral, Antivert, D-vert, Dramamine II \| access-date = 7 November 2010 \| work = MedicineNet }}</ref>

	==~~=Drowsiness=~~==		== Pharmacology ==
			=== Pharmacodynamics ===
	Drowsiness may result as a side effect of taking meclizine. Users are advised not to operate heavy machinery while under the influence. The consumption of alcohol while under the influence of meclizine may result in additional drowsiness.
			Meclizine is an antagonist at H<sub>1</sub> receptors (''K''<sub>i</sub> = 250 nM).<ref>{{cite journal \| vauthors = Tran VT, Chang RS, Snyder SH \| title = Histamine H1 receptors identified in mammalian brain membranes with 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 ], ], and ] effects. Its ] and antivertigo effects are not fully understood, but its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and ] stimulation, and it may affect the medullary ].<ref name="Houston_2022" /> The drug has been shown to reduce the magnitude of the ] 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 ].<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 ] at D<sub>1</sub>-like and D<sub>2</sub>-like receptors{{citation needed\|date=September 2015}} but it does not cause ] 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 \| url-status = dead \| 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 effect 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>
	===Special Considerations in the Elderly===
	As with any ] agent, meclizine may cause '''confusion''' or aggravate symptoms in those with ] in the ] population (those greater than 65 years of age). Therefore '''caution''' should be used when administering meclizine to the elderly. <ref>Merck Manuals, Online Medical Library: Meclizine (Drug Information Provided by Lexi-Comp). , revised January 2010, accessed November 7, 2010.</ref>

			=== Pharmacokinetics ===
	==References==
			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 \| pages = 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 ] 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 = \| journal = Journal of Clinical Chemistry and Clinical Biochemistry. Zeitschrift Fur Klinische Chemie und Klinische Biochemie \| 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 \| pmid = 14269614 }}</ref>
	{{reflist}}

	==~~External links~~==		==Chemistry==
			Meclizine is a ] (nonselective ]) of the ] class. It is structurally and pharmacologically similar to ], ], and ].
	*
	*
	*

			===Synthesis===
			(4-Chlorophenyl)-phenylmethanol is halogenated with ] before adding acetylpiperazine. The acetyl group is cleaved with diluted ]. 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>

			]

			Alternatively, the last step can be replaced by a reductive N-alkylation with 3-methylbenzaldehyde. The reductive agent is ], and ] is used as a ].<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>

			]

			Meclizine is obtained and used as a ], a 1:1 mixture of the two ]s. Drug forms contain the racemic dihydrochloride.{{fact\|date=August 2020}}

			== Society and culture ==
			=== Brand names ===
			Meclizine is an ].<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 ] (2/3). In Canada, Antivert Tab was a combination of meclizine and ].<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}}

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Latest revision as of 07:08, 30 September 2024

Chemical compound "Bonine" and "Dramamine II" redirect here. For the surname, see Bonine (surname). For other uses, see Dramamine (disambiguation).

Pharmaceutical compound

Meclizine
Clinical data

Trade names	Bonine, Antivert, others
Other names	Meclozine
AHFS/Drugs.com	Monograph
MedlinePlus	a682548
License data	US DailyMed: Meclizine
Routes of administration	By mouth, under the tongue, in the cheek
ATC code	R06AE05 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: OTC US: OTC
Pharmacokinetic data
Bioavailability	22 - 32%
Metabolism	Liver (CYP2D6)
Elimination half-life	5-6 hours
Identifiers
IUPAC name (RS)-1--4-(3-methylbenzyl)piperazine
CAS Number	569-65-3
PubChem CID	4034
IUPHAR/BPS	2757
DrugBank	DB00737
ChemSpider	3894
UNII	3L5TQ84570
KEGG	D08163 D01317
ChEMBL	ChEMBL1623
CompTox Dashboard (EPA)	DTXSID0023242
ECHA InfoCard	100.008.477
Chemical and physical data
Formula	C₂₅H₂₇ClN₂
Molar mass	390.96 g·mol
3D model (JSmol)	Interactive image
Boiling point	230 °C (446 °F)
SMILES Clc1ccc(cc1)C(c2ccccc2)N3CCN(CC3)Cc4cccc(c4)C
InChI InChI=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 Key:OCJYIGYOJCODJL-UHFFFAOYSA-N
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Meclizine, sold under the brand name Bonine, among others, is an antihistamine used to treat motion sickness and dizziness (vertigo). It is taken by mouth. Effects generally begin in an hour and last for up to a day.

Common side effects include sleepiness and dry mouth. Serious side effects may include allergic reactions. Use in pregnancy appears safe, but has not been well studied; use in breastfeeding is of unclear safety. It is believed to work in part by anticholinergic and antihistamine mechanisms.

Meclizine was patented in 1951 and came into medical use in 1953. It is available as a generic medication and often over the counter. In 2022, it was the 129th most commonly prescribed medication in the United States, with more than 4 million prescriptions.

Medical uses

Meclizine is used to treat symptoms of motion sickness.

Motion sickness

Meclizine is effective in inhibiting nausea, vomiting, and dizziness caused by motion sickness.

The drug is safe for treating nausea in pregnancy and is a first-line therapy for this use. Meclizine may not be strong enough for especially sickening motion stimuli, and second-line defenses should be tried in those cases.

Vertigo

Meclizine may be used to treat vertigo, such as in those with Ménière's disease.

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. 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.

Pharmacology

Pharmacodynamics

Meclizine is an antagonist at H₁ receptors (K_i = 250 nM). 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. The drug has been shown to reduce the magnitude of the vestibulo-ocular reflex in healthy volunteers. At the same time the drug was found to have only a small (and statistically insignificant) effect on the motion sensitivity of the utricles. 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.

Meclizine also has been reported to be a weak dopamine antagonist at D₁-like and D₂-like receptors but it does not cause catalepsy in mice, perhaps because of its anticholinergic activity. The drug does not effect dopamine or serotonin reuptake.

Pharmacokinetics

Meclizine reaches peak plasma concentration in about 1.5 hours and has an elimination half-life of 5-6 hours. Despite its relatively short half-life, the drug is reported to remain effective for motion sickness for 12 - 24 hours. 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. In children it has been found that taking meclizine with food increases its bioavailability slightly. It is metabolized in the liver by the CYP2D6 enzyme. Ten metabolites have been identified. In rats, the main metabolite is norchlorcyclizine, which distributes extensively through body tissue.

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.

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.

Meclizine is obtained and used as a racemate, a 1:1 mixture of the two stereoisomers. Drug forms contain the racemic dihydrochloride.

Society and culture

Brand names

Meclizine is an international nonproprietary name.

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.

References

^ Sun J, Liu J, Zhang J, Xia H (June 2021). "Meclizine-loaded nanostructured lipid carriers to manage nausea and vomiting: Oral bioavailability improvement". Journal of Drug Delivery Science and Technology. 63: 102432. doi:10.1016/j.jddst.2021.102432.
^ Wang Z, Lee B, Pearce D, Qian S, Wang Y, Zhang Q, et al. (September 2012). "Meclizine metabolism and pharmacokinetics: formulation on its absorption". Journal of Clinical Pharmacology. 52 (9): 1343–1349. doi:10.1177/0091270011414575. PMID 21903894.
^ "Meclizine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 22 March 2019.
"Meclizine Use During Pregnancy". Drugs.com. Retrieved 3 March 2019.
Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 547. ISBN 9783527607495.
Cappa M, Cianfarani S, Ghizzoni L, Loche S, Maghnie M (2015). Advanced Therapies in Pediatric Endocrinology and Diabetology: Workshop, Rome, October 2014. Karger Medical and Scientific Publishers. p. 101. ISBN 9783318056372.
"The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
"Meclizine Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
^ Houston BT, Chowdhury YS (18 July 2022). "Meclizine". StatPearls . Treasure Island (FL): StatPearls Publishing. PMID 32809480.
"Drugs & Medications". www.webmd.com. Retrieved 28 December 2018.
"Antiemetische Therapie bei Schwangerschaftserbrechen" [Antiemetic therapy in pregnancy]. Arznei-Telegramm (in German). 40: 87–89. 2009.
"Meclozin" [Federal Ministry of Health]. Embryotox (in German). Bundesministerium für Gesundheit.
Lawson BD, McGee HA, Castaneda MA, Golding JF, Kass SJ, McGrath CM (2 December 2009). "Evaluation of several common antimotion sickness medications and recommendations concerning their potential usefulness during special operations". Pensacola, Florida: Naval Aerospace Research Lab. Archived from the original on 27 April 2016. Retrieved 7 February 2016.
Nakashima T, Pyykkö I, Arroll MA, Casselbrant ML, Foster CA, Manzoor NF, et al. (May 2016). "Meniere's disease". Nature Reviews. Disease Primers. 2: 16028. doi:10.1038/nrdp.2016.28. PMID 27170253. S2CID 3987838.
"Meclizine". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases. January 2017. PMID 31643231.
Dahl E, Offer-Ohlsen D, Lillevold PE, Sandvik L (July 1984). "Transdermal scopolamine, oral meclizine, and placebo in motion sickness". Clinical Pharmacology and Therapeutics. 36 (1): 116–120. doi:10.1038/clpt.1984.148. PMID 6734040. S2CID 40691502.
"Meclizine - oral, Antivert, D-vert, Dramamine II". MedicineNet. Retrieved 7 November 2010.
Tran VT, Chang RS, Snyder SH (December 1978). "Histamine H1 receptors identified in mammalian brain membranes with [3H]mepyramine". Proceedings of the National Academy of Sciences of the United States of America. 75 (12): 6290–6294. doi:10.1073/pnas.75.12.6290. PMC 393167. PMID 282646.
^ Weerts AP, De Meyer G, Pauwels G, Vanspauwen R, Dornhoffer JL, Van de Heyning PH, et al. (2012). "Pharmaceutical countermeasures have opposite effects on the utricles and semicircular canals in man". Audiology & Neuro-Otology. 17 (4): 235–242. doi:10.1159/000337273. PMID 22517315.
Wibble T, Engström J, Verrecchia L, Pansell T (August 2020). "The effects of meclizine on motion sickness revisited". British Journal of Clinical Pharmacology. 86 (8): 1510–1518. doi:10.1111/bcp.14257. PMC 7373708. PMID 32077140.
Haraguchi K, Ito K, Kotaki H, Sawada Y, Iga T (June 1997). "Prediction of drug-induced catalepsy based on dopamine D1, D2, and muscarinic acetylcholine receptor occupancies". Drug Metabolism and Disposition. 25 (6): 675–684. PMID 9193868. Archived from the original on 28 August 2021. Retrieved 12 June 2014. "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."
Oishi R, Shishido S, Yamori M, Saeki K (February 1994). "Comparison of the effects of eleven histamine H1-receptor antagonists on monoamine turnover in the mouse brain". Naunyn-Schmiedeberg's Archives of Pharmacology. 349 (2): 140–144. doi:10.1007/BF00169830. PMID 7513381.
"ANTIVERT FDA Drug Facts" (PDF). FDA. Retrieved 18 June 2024.
Kitoh H, Matsushita M, Mishima K, Nagata T, Kamiya Y, Ueda K, et al. (13 April 2020). "Pharmacokinetics and safety after once and twice a day doses of meclizine hydrochloride administered to children with achondroplasia". PLOS ONE. 15 (4): e0229639. Bibcode:2020PLoSO..1529639K. doi:10.1371/journal.pone.0229639. PMC 7153885. PMID 32282831.
Goenechea VS, Rücker G, Brzezinka H, Hoffmann G, Neugebauer M, Glanzmann G (February 1988). "". Journal of Clinical Chemistry and Clinical Biochemistry. Zeitschrift Fur Klinische Chemie und Klinische Biochemie. 26 (2): 105–115. PMID 3367105.
Narrod SA, Wilk AL, King CT (March 1965). "Metabolism of Meclizine in the Rat". The Journal of Pharmacology and Experimental Therapeutics. 147: 380–384. PMID 14269614.
Fuhrkop JH, Li G (2003). Organic Synthesis. Concepts and Methods. Wiley. p. 237. ISBN 978-3-527-30272-7.
US 2709169, Morren H, issued 24 May 1955, assigned to Union Chimique Belge Société Anonyme
Kleemann A, Engel J, Kutscher B, Reichert D (2001). Pharmaceutical Substances. Synthesis, Patents, Applications (4th ed.). Thieme. ISBN 3-13-115134-X.
"Guidelines on the Use of INNs for Pharmaceutical Substances" (PDF). WHO. 1997. Retrieved 1 November 2013.
Wishard D. "Drug card for Meclizine". DrugBank. Canada: University of Alberta. Retrieved 7 November 2010.

Medical uses

v t e Antiemetics (A04)
5-HT₃ serotonin ion channel antagonists	Alosetron Azasetron Bemesetron Cilansetron Clozapine Dazopride Dolasetron Granisetron Lerisetron Mianserin Mirtazapine Olanzapine Ondansetron Palonosetron (+netupitant) Quetiapine Ramosetron Ricasetron Tropisetron Zatosetron
5-HT serotonin G-protein receptor antagonists	Clozapine Cyproheptadine Hydroxyzine Olanzapine Risperidone Ziprasidone
CB₁ agonists (cannabinoids)	Dronabinol Nabilone Tetrahydrocannabinol (cannabis)
D₂/D₃ antagonists	Chlorpromazine Haloperidol Hydroxyzine Metoclopramide Metopimazine Prochlorperazine Thiethylperazine Trimethobenzamide
H₁ antagonists (antihistamines)	Cyclizine Dimenhydrinate Diphenhydramine Hydroxyzine Meclizine Promethazine
mACh antagonists (anticholinergics)	Atropine Diphenhydramine Hydroxyzine (very mild) Hyoscyamine Scopolamine
NK₁ antagonists	Aprepitant Fosaprepitant Maropitant Netupitant Rolapitant
Others	Amisulpride Cerium oxalate Dexamethasone Lorazepam Midazolam Propofol

v t e Antihistamines (R06)
Benzimidazoles (*)	Astemizole Azelastine Bilastine Emedastine Mizolastine Talastine
Diarylmethanes	Diarylmethoxyalkylamines: Bromazine (bromodiphenhydramine) Carbinoxamine Chlorphenoxamine Clemastine Diphenhydramine (+naproxen) Diphenylpyraline Doxylamine Ebastine Orphenadrine Diphenylmethanolpiperidines: Fexofenadine Terfenadine Diphenylmethylpiperazines: Buclizine Cetirizine Levocetirizine Chlorcyclizine Cinnarizine Cyclizine Etodroxizine Hydroxyzine Meclizine Oxatomide Phenylpyridinylpropanamines: Brompheniramine Chlorphenamine Dexbrompheniramine (+pseudoephedrine) Dexchlorpheniramine (+betamethasone) Pheniramine Others: Acrivastine Bamipine Dimetindene Phenyltoloxamine Pyrrobutamine Quifenadine Triprolidine
Ethylenediamines	Antazoline Chloropyramine Histapyrrodine Mepyramine (pyrilamine) Methapyrilene Phenbenzamine Thenalidine Tripelennamine (pyribenzamine)
Tricyclics	Dibenzocycloheptenes: Antidepressants (e.g., amitriptyline) Azatadine Cyproheptadine Deptropine Desloratadine Ketotifen Loratadine Rupatadine Phenothiazines: Alimemazine Fenethazine Hydroxyethylpromethazine Isothipendyl Mequitazine Methdilazine Oxomemazine Promethazine Others: Antidepressants (e.g., doxepin, mirtazapine, trimipramine) Epinastine Latrepirdine Mebhydrolin Olopatadine Perlapine Phenindamine Pimethixene
Others	Phenylpiperazines: Antidepressants (e.g., trazodone) Phenbenzamine
For topical use	Bamipine Chloropyramine Chlorphenoxamine Clemastine Dimetindene Diphenhydramine Doxepin Isothipendyl Mepyramine (pyrilamine) Promethazine

v t e Motion sickness
Types	Airsickness Seasickness Simulator sickness Ski sickness Space adaptation syndrome Virtual reality sickness
Medicine treatment	Bonine Cinnarizine Dramamine Marezine Promethazine Transdermscop
Related	Bárány chair Sickness bag

Hallucinogens

Psychedelics
(5-HT_2A
agonists)

25x-NB	25B-NB 25C-NB
25x-NB3OMe	25B-NB3OMe 25C-NB3OMe 25D-NB3OMe 25E-NB3OMe 25H-NB3OMe 25I-NB3OMe 25N-NB3OMe 25P-NB3OMe 25T2-NB3OMe 25T4-NB3OMe 25T7-NB3OMe 25TFM-NB3OMe
25x-NB4OMe	25B-NB4OMe 25C-NB4OMe 25D-NB4OMe 25E-NB4OMe 25H-NB4OMe 25I-NB4OMe 25N-NB4OMe 25P-NB4OMe 25T2-NB4OMe 25T4-NB4OMe 25T7-NB4OMe 25TFM-NB4OMe
25x-NBF	25B-NBF 25C-NBF 25D-NBF 25E-NBF 25H-NBF 25I-NBF 25P-NBF 25T2-NBF 25T7-NBF 25TFM-NBF
25x-NBMD	25B-NBMD 25C-NBMD 25D-NBMD 25E-NBMD 25F-NBMD 25H-NBMD 25I-NBMD 25P-NBMD 25T2-NBMD 25T7-NBMD 25TFM-NBMD
25x-NBOH	25B-NBOH 25C-NBOH 25CN-NBOH 25D-NBOH 25E-NBOH 25F-NBOH 25H-NBOH 25I-NBOH 25P-NBOH 25T2-NBOH 25T7-NBOH 25TFM-NBOH
25x-NBOMe	25B-NBOMe 25C-NBOMe 25CN-NBOMe 25D-NBOMe 25E-NBOMe 25F-NBOMe 25G-NBOMe 25H-NBOMe 25I-NBOMe 25iP-NBOMe 25N-NBOMe 25P-NBOMe 25T-NBOMe 25T2-NBOMe 25T4-NBOMe 25T7-NBOMe 25TFM-NBOMe
Atypical structures	25B-N1POMe 25B-NAcPip 25B-NB23DM 25B-NB25DM 25C-NBCl 25C-NBOEt 25C-NBOiPr 25I-N2Nap1OH 25I-N3MT2M 25I-N4MT3M 25I-NB34MD 25I-NBAm 25I-NBBr 25I-NBMeOH 25I-NBTFM 2CBCB-NBOMe 2CBFly-NBOMe 4-EA-NBOMe 5-APB-NBOMe 5MT-NBOMe C30-NBOMe DOB-NBOMe DOI-NBOMe FECIMBI-36 MDPEA-NBOMe N-Ethyl-2C-B NBOMe-escaline NBOMe-mescaline ZDCM-04

25x-NMx

N-(2C)-fentanyl

3C-x

4C-x

DOx

HOT-x

MDxx

Mescaline (subst.)

TMAs

TMA
TMA-2
TMA-3
TMA-4
TMA-5
TMA-6

Others

Piperazines

Tryptamines

alpha-alkyltryptamines	4,5-DHP-α-MT 5-MeO-α-ET 5-MeO-α-MT α-ET α-MT
x-DALT	(Daltocin) 4-HO-DALT (Daltacetin) 4-AcO-DALT 5-MeO-DALT DALT
x-DET	(Ethacetin) 4-AcO-DET (Ethocin) 4-HO-DET 5-MeO-DET (T-9) DET (Ethocybin) 4-PO-DET
x-DiPT	(Ipracetin) 4-AcO-DiPT (Iprocin) 4-HO-DiPT 5-MeO-DiPT DiPT
x-DMT	4,5-DHP-DMT 2,N,N-TMT 4-AcO-DMT 4-HO-5-MeO-DMT 4,N,N-TMT 4-Propionyloxy-DMT 5,6-diBr-DMT 5-AcO-DMT 5-Bromo-DMT 5-MeO-2,N,N-TMT 5-MeO-4,N,N-TMT 5-MeO-α,N,N-TMT 5-MeO-DMT 5-N,N-TMT 7,N,N-TMT α,N,N-TMT (Bufotenin) 5-HO-DMT DMT Norbaeocystin (Psilocin) 4-HO-DMT (Psilocybin) 4-PO-DMT
x-DPT	(Depracetin) 4-AcO-DPT (Deprocin) 4-HO-DPT 5-MeO-DPT (The Light) DPT
Ibogaine-related	18-MAC 18-MC Coronaridine Ibogaine Ibogamine ME-18-MC Noribogaine Tabernanthine Voacangine
x-MET	(Metocin) 4-HO-MET (Metocetin) 4-AcO-MET 5-MeO-MET MET
x-MiPT	(Mipracetin) 4-AcO-MiPT (Miprocin) 4-HO-MiPT 5-Me-MiPT (Moxy) 5-MeO-MiPT MiPT
Others	4-HO-DBT 4-HO-EPT 4-HO-McPT (Lucigenol) 4-HO-MPMI (Meprocin) 4-HO-MPT 5-MeO-EiPT 5-MeO-MALT 5-MeO-MPMI Aeruginascin Baeocystin DBT DCPT EiPT EPT MPT PiPT

Others

AL-38022A
ALPHA
Dimemebfe
Efavirenz
Glaucine
Lorcaserin
M-ALPHA
RH-34
Also empathogens in general (e. g.: 5-APB, 5-MAPB, 6-APB and other substituted benzofurans).

Dissociatives
(NMDAR
antagonists)

Arylcyclo‐
hexylamines

Ketamine-related	2-Fluorodeschloroketamine Arketamine ((R)-ketamine) Deschloroketamine Ethketamine (N-Ethylnorketamine) Esketamine ((S)-ketamine) Ketamine Methoxetamine Methoxmetamine Methoxyketamine MXiPr Norketamine Tiletamine
PCP-related	2'-Oxo-PCE 3-HO-PCE 3-HO-PCP 3-MeO-PCE 3-MeO-PCMo 3-MeO-PCP 3-MeO-PCPr 3-MeO-PCPy 4-MeO-PCP BDPC Dieticyclidine (PCDE) Eticyclidine (PCE) PCPr Phencyclidine (PCP) Rolicyclidine (PCPy) Tenocyclidine (TCP)
Others	BTCP Gacyclidine PRE-084

Adamantanes

Diarylethylamines

Morphinans

Others

Deliriants
(mAChR
antagonists)

Others

Cannabinoids
(CB₁ agonists)

Natural

Synthetic

AM-x	AM-087 AM-251 AM-279 AM-281 AM-356 AM-374 AM-381 AM-404 AM-411 AM-630 AM-661 AM-678 AM-679 AM-694 AM-735 AM-855 AM-881 AM-883 AM-905 AM-906 AM-919 AM-926 AM-938 AM-1116 AM-1172 AM-1220 AM-1221 AM-1235 AM-1241 AM-1248 AM-1710 AM-1714 AM-1902 AM-2201 AM-2212 AM-2213 AM-2232 AM-2233 AM-2389 AM-3102 AM-4030 AM-4054 AM-4056 AM-4113 AM-6545
CP x	CP 47,497 CP 55,244 CP 55,940 (±)-CP 55,940 (+)-CP 55,940 (-)-CP 55,940
HU-x	HU-210 HU-211 HU-239 HU-243 HU-308 HU-320 HU-331 HU-336 HU-345
JWH-x	JWH-007 JWH-015 JWH-018 JWH-019 JWH-030 JWH-047 JWH-048 JWH-051 JWH-057 JWH-073 JWH-081 JWH-098 JWH-116 JWH-120 JWH-122 JWH-133 JWH-139 JWH-147 JWH-148 JWH-149 JWH-149 JWH-161 JWH-164 JWH-166 JWH-167 JWH-171 JWH-175 JWH-176 JWH-181 JWH-182 JWH-184 JWH-185 JWH-192 JWH-193 JWH-194 JWH-195 JWH-196 JWH-197 JWH-198 JWH-199 JWH-200 JWH-203 JWH-205 JWH-210 JWH-210 JWH-213 JWH-220 JWH-229 JWH-234 JWH-249 JWH-250 JWH-251 JWH-253 JWH-258 JWH-300 JWH-302 JWH-307 JWH-336 JWH-350 JWH-359 JWH-387 JWH-398 JWH-424
Misc. designer cannabinoids	4-HTMPIPO 5F-AB-FUPPYCA 5F-AB-PINACA 5F-ADB 5F-ADB-PINACA 5F-ADBICA 5F-AMB 5F-APINACA 5F-CUMYL-PINACA 5F-NNE1 5F-PB-22 5F-SDB-006 A-796,260 A-836,339 AB-001 AB-005 AB-CHFUPYCA AB-CHMINACA AB-FUBINACA AB-PINACA ADAMANTYL-THPINACA ADB-CHMINACA ADB-FUBINACA ADB-PINACA ADBICA ADSB-FUB-187 AMB-FUBINACA APICA APINACA APP-FUBINACA CB-13 CUMYL-PICA CUMYL-PINACA CUMYL-THPINACA DMHP EAM-2201 FAB-144 FDU-PB-22 FUB-144 FUB-APINACA FUB-JWH-018 FUB-PB-22 FUBIMINA JTE 7-31 JTE-907 Levonantradol MDMB-CHMICA MDMB-CHMINACA MDMB-FUBINACA MEPIRAPIM MAM-2201 MDA-19 MN-18 MN-25 NESS-0327 NESS-040C5 Nabilone Nabitan NM-2201 NNE1 Org 28611 Parahexyl PTI-1 PTI-2 PX-1 PX-2 PX-3 QUCHIC QUPIC RCS-4 RCS-8 SDB-005 SDB-006 STS-135 THC-O-acetate THC-O-phosphate THJ-018 THJ-2201 UR-144 WIN 55,212-2 XLR-11

D₂ agonists

Apomorphine
Aporphine
Bromocriptine
Cabergoline
Lisuride
LSD
Memantine
Nuciferine
Pergolide
Phenethylamine
Piribedil
Pramipexole
Ropinirole
Rotigotine
Salvinorin A
Also indirect D₂ agonists, such as dopamine reuptake inhibitors (cocaine, methylphenidate), releasing agents (amphetamine, methamphetamine), and precursors (levodopa).

GABA_A
enhancers

Inhalants
(Mixed MOA)

κOR agonists

Oneirogens

Others

Pharmacodynamics

Histamine receptor modulators

H₁

Agonists

Antagonists

Others: Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, brilaroxazine, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, zotepine)
Phenylpiperazine antidepressants (e.g., hydroxynefazodone, nefazodone, trazodone, triazoledione)
Tetracyclic antidepressants (e.g., amoxapine, loxapine, maprotiline, mianserin, mirtazapine, oxaprotiline)
Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, iprindole, lofepramine, nortriptyline, protriptyline, trimipramine)
Typical antipsychotics (e.g., chlorpromazine, flupenthixol, fluphenazine, loxapine, perphenazine, prochlorperazine, thioridazine, thiothixene)

H₂

Agonists	Amthamine Betazole Dimaprit Histamine HTMT Impromidine L-Histidine UR-AK49
Antagonists	Bisfentidine Burimamide Cimetidine Dalcotidine Donetidine Ebrotidine Etintidine Famotidine Isolamtidine Lafutidine Lamtidine Lavoltidine (loxtidine) Lupitidine Metiamide Mifentidine Niperotidine Nizatidine Osutidine Oxmetidine Pibutidine Quisultazine (quisultidine) Ramixotidine Ranitidine Roxatidine Sufotidine Tiotidine Tuvatidine Venritidine Xaltidine Zolantidine

H₃

Agonists	α-Methylhistamine Cipralisant Histamine Imetit Immepip Immethridine L-Histidine Methimepip Proxyfan
Antagonists	A-349821 A-423579 ABT-239 ABT-652 AZD5213 Bavisant Betahistine Burimamide Ciproxifan Clobenpropit Conessine Enerisant GSK-189254 Impentamine Iodophenpropit Irdabisant JNJ-5207852 NNC 38-1049 PF-03654746 Pitolisant SCH-79687 Thioperamide VUF-5681

H₄

Agonists	4-Methylhistamine α-Methylhistamine Histamine L-Histidine OUP-16 VUF-8430
Antagonists	JNJ-7777120 Mianserin Seliforant Thioperamide Toreforant VUF-6002

See also: Receptor/signaling modulators; Monoamine metabolism modulators; Monoamine reuptake inhibitors

Ion channel modulators

Calcium

VDCCsTooltip Voltage-dependent calcium channels

Blockers

L-type-selective: Dihydropyridines: Amlodipine
Aranidipine
Azelnidipine
Barnidipine
Clevidipine
Cronidipine
Darodipine
Dexniguldipine
Elgodipine
Elnadipine
Felodipine
Flordipine
Furnidipine
Iganidipine
Isradipine
Lacidipine
Lemildipine
Lercanidipine
Levamlodipine
Levniguldipine
Manidipine
Mepirodipine
Mesudipine
Nicardipine
Nifedipine
Niguldipine
Niludipine
Nilvadipine
Nimodipine
Nisoldipine
Nitrendipine
Olradipine
Oxodipine
Palonidipine
Pranidipine
Ryodipine (riodipine)
Sagandipine
Sornidipine
Teludipine
Tiamdipine
Trombodipine
Vatanidipine; Diltiazem derivatives: Clentiazem
Diltiazem
Iprotiazem
Nictiazem
Siratiazem; Phenylalkylamines: Anipamil
Dagapamil
Devapamil
Dexverapamil
Emopamil
Etripamil
Falipamil
Gallopamil
Levemopamil
Nexopamil
Norverapamil
Ronipamil
Tiapamil
Verapamil; Others: AH-1058
Brinazarone
Budiodarone
Celivarone
Cyproheptadine
Dronedarone
Fantofarone
SR-33805
Tetrahydropalmatine

R-type-selective: SNX-482

α₂δ subunit-selective (gabapentinoids): 4-Methylpregabalin
Arbaclofen
Arbaclofen placarbil
Atagabalin
Baclofen
Gabapentin
Gabapentin enacarbil
Imagabalin
Mirogabalin
PD-200,347
PD-217,014
PD-299,685
Phenibut
Pregabalin

Activators

L-type-selective: Bay K8644

Potassium

VGKCsTooltip Voltage-gated potassium channels

Blockers

hERG (KCNH2, K_v11.1)-specific: Ajmaline
Amiodarone
AmmTX3
Astemizole
Azaspiracid
AZD1305
Azimilide
Bedaquiline
BeKm-1
BmTx3
BRL-32872
Chlorpromazine
Cisapride
Clarithromycin
Darifenacin
Dextropropoxyphene
Diallyl trisulfide
Domperidone
E-4031
Ergtoxins
Erythromycin
Gigactonine
Haloperidol
Ketoconazole
Norpropoxyphene
Orphenadrine
Pimozide
PNU-282,987
Promethazine
Quinidine
Ranolazine
Roxithromycin
Sertindole
Solifenacin
Tamulotoxin
Terodiline
Terfenadine
Thioridazine
Tolterodine
Vanoxerine
Vernakalant

Activators

KCNQ (K_v7)-specific: Flupirtine
Retigabine

IRKsTooltip Inwardly rectifying potassium channel

Blockers

K_ATPTooltip ATP-sensitive potassium channel-specific: Acetohexamide
Carbutamide
Chlorpropamide
Glibenclamide (glyburide)
Glibornuride
Glicaramide
Gliclazide
Glimepiride
Glipizide
Gliquidone
Glisoxepide
Glyclopyramide
Glycyclamide
Metahexamide
Mitiglinide
Nateglinide
Repaglinide
Tolazamide
Tolbutamide

GIRKTooltip G protein-coupled inwardly rectifying potassium channel-specific: Barium
Caramiphen
Cloperastine
Clozapine
Dextromethorphan
Ethosuximide
Ifenprodil
Tertiapin
Tipepidine

Activators

K_ATPTooltip ATP-sensitive potassium channel-specific: Aprikalim
Bimakalim
Cromakalim
Diazoxide
Emakalim
Levcromakalim
Mazokalim
Minoxidil
Minoxidil sulfate
Naminidil
Nicorandil
Pinacidil
Rilmakalim
Sarakalim

GIRKTooltip G protein-coupled inwardly rectifying potassium channel-specific: ML-297 (VU0456810)

K_CaTooltip Calcium-activated potassium channel

Blockers	BK_Ca-specific: Ethanol (alcohol) GAL-021
Activators	BK_Ca-specific: Flufenamic acid Meclofenamic acid Niflumic acid Nimesulide Rottlerin (mallotoxin) Tolfenamic acid

K2PsTooltip Tandem pore domain potassium channel

Blockers	12-O-Tetradecanoylphorbol-13-acetate Arachidonic acid Fluoxetine Norfluoxetine
Activators	Riluzole

Sodium

VGSCsTooltip Voltage-gated sodium channels

Blockers

Antianginals: Ranolazine

Local anesthetics: pFBT
Amylocaine
Articaine
Benzocaine
Bupivacaine (Levobupivacaine, Ropivacaine)
Butacaine
Butamben
Chloroprocaine
Cinchocaine
Cocaine
Cyclomethycaine
Dimethocaine
Diphenhydramine
Etidocaine
Hexylcaine
Iontocaine
Lidocaine
Mepivacaine
Meprylcaine
Metabutoxycaine
Orthocaine
Piperocaine
Prilocaine
Procaine
Propoxycaine
Proxymetacaine
Risocaine
Tetracaine
Trimecaine

Activators

Aconitine
Atracotoxins (ω-Atracotoxin, Robustoxin, Versutoxin)
Batrachotoxin
Ciguatoxins
Grayanotoxins
Poneratoxin

ENaCTooltip Epithelial sodium channel

Blockers	Amiloride Benzamil Triamterene
Activators	Solnatide

ASICsTooltip Acid-sensing ion channel

Blockers	A-317567 Amiloride Aspirin Ibuprofen PcTX1

Chloride

CaCCsTooltip Calcium-activated chloride channel

Blockers	Crofelemer DIDS Ethacrynic acid Flufenamic acid Fluoxetine Furosemide Glibenclamide Mefloquine Mibefradil Niflumic acid
Activators	Carbachol

CFTRTooltip Cystic fibrosis transmembrane conductance regulator

Blockers	Glibenclamide Lonidamine Piretanide
Activators	1,7-Phenanthroline 1,10-Phenanthroline 4,7-Phenanthroline 7,8-Benzoquinoline Ivacaftor Phenanthridine