Meclizine

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Meclizine
Meclizine.svg
Clinical data
Trade names Bonine, Antivert, others
Other namesMeclozine
AHFS/Drugs.com Monograph
MedlinePlus a682548
License data
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
Metabolism Liver
Elimination half-life 6 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 InfoCard 100.008.477 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C25H27ClN2
Molar mass 390.96 g·mol−1
3D model (JSmol)
Boiling point 230 °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 Yes check.svgY
  • Key:OCJYIGYOJCODJL-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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

Contents

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; 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 2020, it was the 142nd most commonly prescribed medication in the United States, with more than 4 million prescriptions. [5] [6]

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. [7]

Motion sickness

Meclizine is effective in inhibiting nausea, vomiting, and dizziness caused by motion sickness. [8]

The drug is safe for treating nausea in pregnancy and is a first-line therapy for this use. [9] [10] 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. [11]

Vertigo

Meclizine may be used to treat vertigo, such as in those with Ménière's disease. [12] [13]

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. [14] 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. [15]

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. [1]

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. [16]

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. [7] It has, however, been suggested that meclizine only has an inhibitory effect under normal viewing-circumstances, as the drug has been shown to enhance an isolated vestibular response. 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. [17] 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. [18]

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).[ citation needed ] It is used as an antivertigo/antiemetic agent, specifically in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. [7] 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-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. [19]

Meclozine synthesis 01.svg

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. [20] [21]

Meclozine synthesis 02.svg

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

Names

Meclizine is an international nonproprietary name. [22]

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. [23]

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." [18]

Related Research Articles

<span class="mw-page-title-main">Motion sickness</span> Nausea caused by motion or perceived motion

Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include dehydration, electrolyte problems, or a lower esophageal tear.

An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may be used for severe cases of gastroenteritis, especially if the patient is dehydrated.

H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.

<span class="mw-page-title-main">Diphenhydramine</span> Antihistamine medication

Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremors in parkinsonism, and nausea. It is taken by mouth, injected into a vein, injected into a muscle, or applied to the skin. Maximal effect is typically around two hours after a dose, and effects can last for up to seven hours.

<span class="mw-page-title-main">Dimenhydrinate</span> Anti-emetic and antihistamine medication

Dimenhydrinate, sold under the brand name Dramamine, among others, is an over-the-counter medication used to treat motion sickness and nausea. Dimenhydrinate is a theoclate salt composed of diphenhydramine and 8-chlorotheophylline in a 1:1 ratio.

Postoperative nausea and vomiting (PONV) is the phenomenon of nausea, vomiting, or retching experienced by a patient in the post-anesthesia care unit (PACU) or within 24 hours following a surgical procedure. PONV affects about 10% of the population undergoing general anaesthesia each year. PONV can be unpleasant and lead to a delay in mobilization and food, fluid, and medication intake following surgery.

<span class="mw-page-title-main">Hydroxyzine</span> Antihistamine drug

Hydroxyzine, sold under the brand names Atarax and Vistaril among others, is an antihistamine medication. It is used in the treatment of itchiness, insomnia, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or injection into a muscle.

<span class="mw-page-title-main">Cetirizine</span> Antihistamine medication

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<span class="mw-page-title-main">Promethazine</span> Pharmaceutical drug

Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people who are agitated or anxious, an effect that has led to some recreational use. Promethazine is taken by mouth (oral), as a rectal suppository, or by injection into a muscle (IM).

Airsickness is a specific form of motion sickness which is induced by air travel and is considered a normal response in healthy individuals. Airsickness occurs when the central nervous system receives conflicting messages from the body affecting balance and equilibrium. Whereas commercial airline passengers may simply feel poorly, the effect of airsickness on military aircrew may lead to a decrement in performance and adversely affect the mission.

<span class="mw-page-title-main">Doxylamine</span> First-generation antihistamine used as a short-term sedative and hypnotic (sleep aid)

Doxylamine, sold under the brand name Unisom among others, is an antihistamine medication which is used in the treatment of insomnia and allergies. It is also used to treat morning sickness in pregnant women in combination with pyridoxine (vitamin B6). Doxylamine is available over-the-counter, and is used in nighttime cold medicines, such as NyQuil, as well as in pain medications containing acetaminophen and codeine, to help with sleep. The medication is taken by mouth.

<span class="mw-page-title-main">Levocetirizine</span> Antihistamine drug

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<span class="mw-page-title-main">Hyoscine butylbromide</span> Anticholinergic medication

Hyoscine butylbromide, also known as scopolamine butylbromide and sold under the brandname Buscopan among others, is an anticholinergic medication used to treat abdominal pain, esophageal spasms, bladder spasms, biliary colic, and renal colic. It is also used to improve excessive respiratory secretions at the end of life. Hyoscine butylbromide can be taken by mouth, injection into a muscle, or into a vein.

<span class="mw-page-title-main">Cinnarizine</span> Antihistamine and calcium channel blocker medication

Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. It is prescribed for nausea and vomiting due to motion sickness or other sources such as chemotherapy, vertigo, or Ménière's disease.

<span class="mw-page-title-main">Cyclizine</span> Antiemetic/motion sickness

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<span class="mw-page-title-main">8-Chlorotheophylline</span> Chemical compound

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References

  1. 1 2 3 4 5 6 7 8 "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 J, Ganellin CR (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. ↑ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  6. ↑ "Meclizine - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  7. 1 2 3 Houston BT, Chowdhury YS (18 July 2022). "Meclizine". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID   32809480.
  8. ↑ "Drugs & Medications". www.webmd.com. Retrieved 28 December 2018.
  9. ↑ "Antiemetische Therapie bei Schwangerschaftserbrechen" [Antiemetic therapy in pregnancy]. Arznei-Telegramm (in German). 40: 87–89. 2009.
  10. ↑ "Meclozin" [Federal Ministry of Health]. Embryotox (in German). Bundesministerium für Gesundheit.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ "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.
  14. ↑ 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.
  15. ↑ "Meclizine - oral, Antivert, D-vert, Dramamine II". MedicineNet. Retrieved 7 November 2010.
  16. ↑ "Meclizine". Drug Information Provided by Lexi-Comp. January 2010. Archived from the original on 22 August 2009. Retrieved 7 November 2010– via Merck Manuals, Online Medical Library.
  17. ↑ 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.
  18. 1 2 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.
  19. ↑ Fuhrkop JH, Li G (2003). Organic Synthesis. Concepts and Methods. Wiley. p. 237. ISBN   978-3-527-30272-7.
  20. ↑ US 2709169,Morren H,issued 24 May 1955, assigned to Union Chimique Belge Société Anonyme
  21. ↑ Kleemann A, Engel J, Kutscher B, Reichert D (2001). Pharmaceutical Substances. Synthesis, Patents, Applications (4th ed.). Thieme. ISBN   3-13-115134-X.
  22. ↑ "Guidelines on the Use of INNs for Pharmaceutical Substances" (PDF). WHO. 1997. Retrieved 1 November 2013.
  23. ↑ Wishard D. "Drug card for Meclizine". DrugBank. Canada: University of Alberta. Retrieved 7 November 2010.
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