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an antihistamine (trade name Antivert) used to treat or prevent motion sickness (同)meclizine_hydrochloride, Antivert

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/08/27 12:05:30」(JST)

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Meclizine (INN,^[1] or meclozine) is an antihistamine considered to be an antiemetic. It is sold under the brand names Bonine, Bonamine, Antivert, Postafen, Sea Legs, and Dramamine (Less Drowsy Formulation). Emesafene is a combination of meclizine (1/3) and pyridoxine (2/3). In Canada, Antivert Tab (which is no longer available) was a combination of meclizine and nicotinic acid.^[2]

Classification

Meclizine is a first-generation antihistamine of the piperazine class. It is structurally and pharmacologically similar to buclizine, cyclizine, and hydroxyzine, but has a shorter half-life of six hours compared to cyclizine and hydroxyzine with about 20 hours (though half-life should not be confused with duration). It is used as an antivertigo/antiemetic agent, specifically in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness.^[3] Meclizine is sometimes combined with opioids, especially ones of the open-chain class like methadone, dextropropoxyphene, and dipipanone (originally combined with meclizine's parent drug cyclizine, the brand name of this combination is Diconal).

Mechanism of action

Meclizine is an antagonist at H₁ receptors. 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.^[3] Meclizine also is a dopamine antagonist at D1-like and D2-like receptors, but does not cause catalepsy^{[note 1]} in mice, perhaps because of its anticholinergic activity.^[4]

Uses

Meclizine is approved by the U.S. Food and Drug Administration (FDA) to treat symptoms of motion sickness and for management of vertigo that stems from diseases affecting the vestibular system. 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 (older than 65 years) because of increased risk of confusion and amnesia.^[5]

Motion sickness

Meclizine is effective in inhibiting the symptoms of motion sickness, such as nausea, vomiting, and dizziness. The recommended dose is 25–50 mg orally, taken one hour before travel. The dose may be repeated every 6 hours as needed.^[3]

The drug is also safe for treating nausea in pregnancy^[6] and is a first-line therapy for this use.^[7]^[8] Doxylamine is similarly safe.

Vertigo

Meclizine may be effective in relieving vertigo experienced as a result of inner ear infections or other conditions. The recommended dose is 25–100 mg per day orally, in divided doses.^[3]

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.^[9] 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.^[10]

Drowsiness

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.

Special considerations in the elderly

As with any anticholinergic agent, meclizine may cause confusion or aggravate symptoms in those with dementia in the geriatric population (older than 65 years). Therefore caution should be used when administering meclizine to the elderly.^[11]

Synthesis

(4-Chlorphenyl)-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.^[12]

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.^[13]^[14]

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

Notes

^ "[C]atalepsy 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."^[4]

References

^ Guidelines on the Use of INNs for Pharmaceutical Substances (1997). Accessed November, 2013 "Guidance on INN." WHO.
^ DrugBank. Drugbank: Drug card for Meclizine David Wishard: University of Alberta, Canada. Accessed November 7, 2010.
^ ^a ^b ^c ^d Clinical Pharmacology. Clinical Pharmacology, revised November 20, 2009, accessed November 7, 2010.^{[broken citation]}
^ ^a ^b Haraguchi K, Ito K, Kotaki H, Sawada Y, Iga T (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. Retrieved 2014-06-12.
^ MICROMEDEX 2.0. Accessed November 7, 2010.^{[broken citation]}
^ Källén B, Mottet I (2003). "Delivery outcome after the use of meclizine in early pregnancy". European Journal of Epidemiology 18 (7): 665–669. doi:10.1023/a:1024891618953. PMID 12952140. Retrieved 2010-09-17.
^ "Antiemetische Therapie bei Schwangerschaftserbrechen" [Antiemetic therapy in pregnancy]. Arznei-Telegramm (in German) 40: 87–89. 2009.
^ Embryotox: Meclozin (German)
^ Dahl E, Offer-Ohlsen D, Lillevold PE, Sandvik L. Transdermal scopolamine, oral meclizine, and placebo in motion sickness. Clinical Pharmacology And Therapeutics [Clin Pharmacol Ther] 1984 Jul; Vol. 36 (1), pp. 116-20. Available from: MEDLINE: Ipswich, MA. PMID 6734040
^ Meclizine - oral, Antivert, D-vert, Dramamine II. Accessed November 7, 2010.
^ Merck Manuals, Online Medical Library: Meclizine (Drug Information Provided by Lexi-Comp), revised January 2010, accessed November 7, 2010.
^ J.-H. Fuhrkop, G. Li (2003). Organic Synthesis. Concepts and Methods. Wiley. p. 237. ISBN 978-3-527-30272-7.
^ US 2 709 169 (UCB, 1955)
^ A. Kleemann, J. Engel, B. Kutscher, D. Reichert (2001). Pharmaceutical Substances. Synthesis, Patents, Applications (4 ed.). Thieme. ISBN 3-13-115134-X.

External links

University of Berlin's Institute of Biochemistry
Numark Pharmacies Information Page on Meclizine
Rxlist Medical Dictionary

UpToDate Contents

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1. 回転性めまいの治療 treatment of vertigo
2. 乗物酔い motion sickness
3. コーガン症候群 cogans syndrome
4. 妊娠の悪心および嘔吐の治療および転帰 treatment and outcome of nausea and vomiting of pregnancy
5. メニエール病 meniere disease

English Journal

A stability-indicating RP-HPLC method for the quantitative analysis of meclizine hydrochloride in tablet dosage form.

Peraman R1, Manikala M2, Kondreddy VK1, Yiragamreddy PR1.
Journal of chromatographic science.J Chromatogr Sci.2015 May-Jun;53(5):793-9. doi: 10.1093/chromsci/bmu127. Epub 2015 Feb 1.
A specific stability-indicating reversed-phase high-performance liquid chromatographic method was developed and validated for the estimation of meclizine hydrochloride (MEC) in tablet dosage form. The HPLC method has shown adequate separation of MEC from their degradation products. The separation wa
PMID 25644814

Meclozine promotes longitudinal skeletal growth in transgenic mice with achondroplasia carrying a gain-of-function mutation in the FGFR3 gene.

Matsushita M1, Hasegawa S, Kitoh H, Mori K, Ohkawara B, Yasoda A, Masuda A, Ishiguro N, Ohno K.
Endocrinology.Endocrinology.2015 Feb;156(2):548-54. doi: 10.1210/en.2014-1914. Epub 2014 Dec 2.
Achondroplasia (ACH) is one of the most common skeletal dysplasias causing short stature owing to a gain-of-function mutation in the FGFR3 gene, which encodes the fibroblast growth factor receptor 3. We found that meclozine, an over-the-counter drug for motion sickness, inhibited elevated FGFR3 sign
PMID 25456072

Racial differences in anticholinergic use among community-dwelling elders.

Felton M1, Hanlon JT, Perera S, Thorpe JM, Marcum ZA.
The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists.Consult Pharm.2015;30(4):240-5. doi: 10.4140/TCP.n.2015.240.
OBJECTIVE: Few studies have examined racial differences in potentially inappropriate medication use. The objective of this study was to examine racial disparities in using prescription and/or nonprescription anticholinergics, a type of potentially inappropriate medication, over time.DESIGN: Longitud
PMID 25893702

Japanese Journal

Quantification of meclizine in human plasma by high performance liquid chromatography-mass spectrometry

WANG Zhijun,QIAN Shuai,ZHANG Qizhi,CHOW Moses S. S.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 879(1), 95-99, 2011-01-01
NAID 10029025476

ヒスタミンと抗ヒスタミン薬の油水界面におけるイオン移動ボルタンメトリー

塚本龍治,楠文代
分析化学 52(10), 865-871, 2003-10-05
ニトロベンゼン/水の油水界面のイオン移動ボルタンメトリーによって,ヒスタミン及び抗ヒスタミン薬であるdl-クロルフェニラミン,クレマスチン,ジフェンヒドラミン,シプロヘプタジン,メクリジン,プロメタジン,ケトチフェン及びテルフェナジンの油水界面におけるイオン移動と吸着を検討した.ボルタモグラム上に,抗ヒスタミン薬はヒスタミンに比べ負電位側で水相から油相への移動による陽極波が現れ,また,電気毛管曲線 …
NAID 110002907429

Pharmaceutical Properties of Freeze-Dried Formulations of Egg Albumin, Several Drugs and Olive Oil

TSUJI Yasuhiro,KAKEGAWA Hisao,MIYATAKA Hideki,NISHIKI Mayumi,MATSUMOTO Hitoshi,SATOH Toshio
Biological & pharmaceutical bulletin 19(4), 636-640, 1996-04-15
… The freeze-dried ternary formulations of meclizine (MZ, an anti-motion sickness drug), prednisolone (PRED, an anti-inflammatory drug) and norfloxacin (NFLX, an anti-microbial drug) which are poorly water-soluble and are low bioavailability drugs, were prepared using egg albumin and olive oil. …
NAID 110003641230

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★リンクテーブル★

リンク元	「メクリジン」「meclozine」
拡張検索	「meclizine hydrochloride」

「メクリジン」

Meclizine
Systematic (IUPAC) name
	(RS)-1-[(4-chlorophenyl)(phenyl)methyl]-4-(3-methylbenzyl)piperazine
Clinical data
MedlinePlus	a682548
Pregnancy cat.	B (US)
Legal status	Prescription Only (S4) (AU) OTC (CA) OTC (US)
Routes	Oral, sublingual/buccal
Pharmacokinetic data
Metabolism	hepatic
Half-life	6 hours
Identifiers
CAS number	569-65-3
ATC code	R06AE05
PubChem	CID 4034
IUPHAR ligand	2757
DrugBank	DB00737
ChemSpider	3894
UNII	3L5TQ84570
ChEMBL	CHEMBL1623
Chemical data
Formula	C25H27ClN2
Mol. mass	390.948 g/mol
	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 ;
Physical data
Boiling point	230 °C (446 °F)
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