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]
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 2021, it was the 136th most commonly prescribed medication in the United States, with more than 4million 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]
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]
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]
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 (which is no longer available) was a combination of meclizine and
nicotinic acid.[23]
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."[18]
^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.
^"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.