Meclizine, sold under the brand name Bonine, among others, is an antihistamine used to treat motion sickness and dizziness (vertigo).[3] It is taken by mouth.[3] Effects generally begin in an hour and last for up to a day.[3]
Meclizine was patented in 1951 and came into medical use in 1953.[5] It is available as a generic medication and often over the counter.[3][6] In 2021, it was the 136th most commonly prescribed medication in the United States, with more than 4million prescriptions.[7][8]
Meclizine is effective in inhibiting nausea, vomiting, and dizziness caused by motion sickness.[10]
The drug is safe for treating nausea in pregnancy and is a first-line therapy for this use.[11][12] Meclizine may not be strong enough for especially sickening motion stimuli, and second-line defenses should be tried in those cases.[13]
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.[16] 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.[17]
Meclizine is an antagonist at H1 receptors (Ki = 250 nM).[18] 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.[9] The drug has been shown to reduce the magnitude of the vestibulo-ocular reflex in healthy volunteers.[19] At the same time the drug was found to have only a small (and statistically insignificant) effect on the motion sensitivity of the utricles.[19] 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.[20]
Meclizine also has been reported to be a weak dopamine antagonist at D1-like and D2-like receptors[citation needed] but it does not cause catalepsy in mice, perhaps because of its anticholinergic activity.[21] The drug does not effect dopamine or serotonin reuptake.[22]
Meclizine reaches peak plasma concentration in about 1.5 hours and has an elimination half-life of 5-6 hours.[2] Despite its relatively short half-life, the drug is reported to remain effective for motion sickness for 12 - 24 hours.[23] 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.[1] In children it has been found that taking meclizine with food increases its bioavailability slightly.[24] It is metabolized in the liver by the CYP2D6 enzyme.[2] Ten metabolites have been identified.[25] In rats, the main metabolite is norchlorcyclizine, which distributes extensively through body tissue.[26]
(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.[27]
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.[28][29]
Meclizine is obtained and used as a racemate, a 1:1 mixture of the two stereoisomers. Drug forms contain the racemic dihydrochloride.[citation needed]
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.[31]
^ abSun 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.
^ abcWang 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. PMID21903894.
^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. PMID27170253. S2CID3987838.
^"Meclizine". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases. January 2017. PMID31643231.
^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. PMID6734040. S2CID40691502.
^ abWeerts 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. PMID22517315.
^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. PMID7513381.
^Goenechea VS, Rücker G, Brzezinka H, Hoffmann G, Neugebauer M, Glanzmann G (February 1988). "[Biotransformation of meclozine in the human body]". Journal of Clinical Chemistry and Clinical Biochemistry. Zeitschrift Fur Klinische Chemie und Klinische Biochemie. 26 (2): 105–115. PMID3367105.
^Narrod SA, Wilk AL, King CT (March 1965). "Metabolism of Meclizine in the Rat". The Journal of Pharmacology and Experimental Therapeutics. 147: 380–384. PMID14269614.
^Fuhrkop JH, Li G (2003). Organic Synthesis. Concepts and Methods. Wiley. p. 237. ISBN978-3-527-30272-7.
^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. ISBN3-13-115134-X.
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