Meclizine

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Meclizine
Clinical data
Trade namesBonamine, Antivert, others
Other namesMeclozine
AHFS/Drugs.comMonograph
MedlinePlusa682548
Routes of
administration		By mouth, under the tongue, in the cheek
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: OTC
  • US: OTC
Pharmacokinetic data
MetabolismLiver
Elimination half-life6 hours
Identifiers
  • (RS)-1-[(4-chlorophenyl)(phenyl)methyl]-4-(3-methylbenzyl)piperazine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.008.477 Edit this at Wikidata
Chemical and physical data
FormulaC25H27ClN2
Molar mass390.948 g/mol g·mol−1
3D model (JSmol)
Boiling point230 °C (446 °F)
  • Clc1ccc(cc1)C(c2ccccc2)N3CCN(CC3)Cc4cccc(c4)C
  • 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 checkY
  • Key:OCJYIGYOJCODJL-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Meclizine, sold under the brand names Bonamine among others, is an antihistamine used to treat motion sickness and symptoms of vertigo.[1] It is taken by mouth.[1] Effects generally begin in an hour and last for up to a day.[1]

Common side effects include sleepiness and dry mouth.[1] Serious side effects may include allergic reactions.[1] Use in pregnancy appears safe but has not been well studied while use in breastfeeding is of unclear safety.[2] It is believed to work in part by anticholinergic and antihistamine mechanisms.[1]

Meclizine was patented in 1951 and came into medical use in 1953.[3] It is available as a generic medication and often over the counter.[1][4] In the United States the wholesale cost per dose is about US$0.03.[5] It is not available in Australia.[6] In 2016 it was the 162nd most prescribed medication in the United States with more than three million prescriptions.[7]

Medical uses

Meclizine is used to treat symptoms of motion sickness. Safety and efficacy in children younger than twelve years of age has not been established; therefore, use in this population is not recommended.[citation needed] Meclizine should be taken with caution in the elderly due to increased risk of confusion and amnesia.[8]

Motion sickness

Meclizine is effective in inhibiting the symptoms of motion sickness, such as nausea, vomiting, and dizziness.[9]

The drug is safe for treating nausea in pregnancy[10] and is a first-line therapy for this use.[11][12] Doxylamine is similarly safe. Meclizine may not be strong enough for especially sickening motion stimuli and second-line defenses should be tried in those cases.[13]

Vertigo

Meclizine is effective in relieving vertigo experienced as a result of inner ear infection or positional or chronic vertigo.[14]

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.[15] 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.[16]

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.

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.[17]

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.[18] Meclizine also is a dopamine antagonist at D1-like and D2-like receptors[citation needed] but does not cause catalepsy[note 1] in mice, perhaps because of its anticholinergic activity.[19]

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, 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.[18] Meclizine is sometimes combined with opioids, especially ones of the open-chain class like methadone, dextropropoxyphene, and dipipanone. Similarly, Diconal is a combination drug containing dipipanone and cyclizine.[citation needed]

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.[20]

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.[21][22]

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

Names

Meclizine is an international nonproprietary name.[23]

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 (which is no longer available) was a combination of meclizine and nicotinic acid.[24]

Notes

  1. ^ "[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."[19]

References

  1. ^ a b c d e f g "Meclizine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 22 March 2019.
  2. ^ "Meclizine Use During Pregnancy". Drugs.com. Retrieved 3 March 2019.
  3. ^ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 547. ISBN 9783527607495.
  4. ^ 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.
  5. ^ "NADAC as of 2019-02-27". Centers for Medicare and Medicaid Services. Retrieved 3 March 2019.
  6. ^ McKenzie, Gayle; Broyles, Bonita; Evans, Mary E.; Page, Rachel; Pleunik, Sussan; Reiss, Barry S. (2016). Pharmacology in Nursing: Australian and New Zealand Edition with Student Resource Access 12 Months. Cengage AU. p. 569. ISBN 9780170362030.
  7. ^ "The Top 300 of 2019". clincalc.com. Retrieved 22 December 2018.
  8. ^ MICROMEDEX 2.0. Accessed November 7, 2010.[full citation needed]
  9. ^ "Drugs & Medications". www.webmd.com. Retrieved 2018-12-28.
  10. ^ Källén B, Mottet I (2003). "Delivery outcome after the use of meclizine in early pregnancy" (PDF). European Journal of Epidemiology. 18 (7): 665–669. doi:10.1023/a:1024891618953. PMID 12952140. Retrieved 2010-09-17.
  11. ^ "Antiemetische Therapie bei Schwangerschaftserbrechen" [Antiemetic therapy in pregnancy]. Arznei-Telegramm (in German). 40: 87–89. 2009.
  12. ^ Embryotox: Meclozin Template:De icon
  13. ^ "Evaluation of Several Common Antimotion Sickness Medications and Recommendations Concerning Their Potential Usefulness During Special Operations". 2009. Retrieved 2016-04-18. {{cite web}}: Cite uses deprecated parameter |authors= (help)
  14. ^ Cohen, Bernard (1 August 1972). "Meclizine and Placebo in Treating Vertigo of Vestibular Origin". Archives of Neurology. 27 (2): 129. doi:10.1001/archneur.1972.00490140033006.
  15. ^ 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
  16. ^ Meclizine - oral, Antivert, D-vert, Dramamine II. Accessed November 7, 2010.
  17. ^ Merck Manuals, Online Medical Library: Meclizine (Drug Information Provided by Lexi-Comp), revised January 2010, accessed November 7, 2010.
  18. ^ a b Clinical Pharmacology. Clinical Pharmacology, revised November 20, 2009, accessed November 7, 2010.[full citation needed]
  19. ^ 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.
  20. ^ Organic Synthesis. Concepts and Methods. Wiley. 2003. p. 237. ISBN 978-3-527-30272-7. {{cite book}}: Cite uses deprecated parameter |authors= (help)
  21. ^ US 2 709 169 (UCB, 1955)
  22. ^ Pharmaceutical Substances. Synthesis, Patents, Applications (4 ed.). Thieme. 2001. ISBN 3-13-115134-X. {{cite book}}: Cite uses deprecated parameter |authors= (help)
  23. ^ Guidelines on the Use of INNs for Pharmaceutical Substances (1997). Accessed November, 2013 "Guidance on INN." WHO.
  24. ^ DrugBank. Drugbank: Drug card for Meclizine David Wishard: University of Alberta, Canada. Accessed November 7, 2010.

External links

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