Meclizine, sold under the brand name Bonine, among others, is an

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...

used to treat

motion sickness 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 d ...

and dizziness (

vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...

). It is taken by mouth. Effects generally begin in an hour and last for up to a day. Common side effects include sleepiness and dry mouth. Serious side effects may include

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

. Use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

appears safe, but has not been well studied while use in

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

is of unclear safety. It is believed to work in part by

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system ...

and

mechanisms. Meclizine was patented in 1951 and came into medical use in 1953. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

and often

over the counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

. In 2020, it was the 142nd most commonly prescribed medication in the United States, with more than 4million prescriptions.

Medical uses

Meclizine is used to treat symptoms of

. Safety and efficacy in children younger than twelve years of age has not been established; therefore, use in this population is not recommended. Meclizine should be taken with caution in the

elderly Old age refers to ages nearing or surpassing the life expectancy of human beings, and is thus the end of the human life cycle. Terms and euphemisms for people at this age include old people, the elderly (worldwide usage), OAPs (British usage ...

due to increased risk of

confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"

and

amnesia Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use ...

Motion sickness

Meclizine is effective in inhibiting nausea, vomiting, and dizziness caused by

. The drug is safe for treating nausea in pregnancy and is a first-line therapy for this use.

Doxylamine Doxylamine, sold under the brand name Unisom among others, is an antihistamine medication which is used in the treatment of insomnia and allergies. In combination with pyridoxine ( vitamin B6), it is also used to treat morning sickness in pre ...

is similarly safe. Meclizine may not be strong enough for especially sickening motion stimuli and second-line defenses should be tried in those cases.

Vertigo

Meclizine may be used to treat

such as in those with

Ménière's disease Ménière's disease (MD) is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Typically, only one ear is affected initial ...

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 Scopolamine, also known as hyoscine, or Devil's Breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is formally used as a medication for treating motion sickness and postoperative nausea and vomiting ...

. 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.

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

agent, meclizine may cause confusion or aggravate symptoms in those with

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

in the

geriatric Geriatrics, or geriatric medicine, is a medical specialty focused on providing care for the unique health needs of older adults. The term ''geriatrics'' originates from the Greek language, Greek γέρων ''geron'' meaning "old man", and ιατ ...

population (older than 65 years). Therefore, caution should be used when administering meclizine to the elderly.

Mechanism of action

Meclizine is an antagonist at H₁ receptors. It possesses

central nervous system depressant A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the l ...

, and

local anesthetic A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general an ...

effects. Its

antiemetic 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 ...

and antivertigo effects are not fully understood, but its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and

vestibular The Vestibular (from pt, vestíbulo, "entrance hall") is a competitive examination and is the primary and widespread entrance system used by Brazilian universities to select the students admitted. The Vestibular usually takes place from Novem ...

stimulation, and it may affect the medullary

chemoreceptor trigger zone The chemoreceptor trigger zone (CTZ) is an area of the medulla oblongata that receives inputs from blood-borne drugs or hormones, and communicates with other structures in the vomiting center to initiate vomiting. The CTZ is located within the area ...

. 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 like motion-sickness arises from a discrepancy between multiple senses, Meclizine most likely affects a wide array of sensory mechanisms related to self-motion. Meclizine also is a

dopamine antagonist A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have ...

at D₁-like and D₂-like receptors but does not cause

catalepsy Catalepsy (from Ancient Greek , , "seizing, grasping") is a nervous condition characterized by muscular rigidity and fixity of posture regardless of external stimuli, as well as decreased sensitivity to pain. Signs and symptoms Symptoms inc ...

in mice, perhaps because of its anticholinergic activity.

Chemistry

Meclizine is a

first-generation antihistamine 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 hi ...

(nonselective H₁ antagonist) of the

piperazine Piperazine () is an organic compound that consists of a six-membered ring containing two nitrogen atoms at opposite positions in the ring. Piperazine exists as small alkaline deliquescent crystals with a saline taste. The piperazines are a broad ...

class. It is structurally and pharmacologically similar to

buclizine Buclizine is an antihistamine and anticholinergic of the diphenylmethylpiperazine group. It is considered to be an antiemetic, similar to meclizine. In the United Kingdom, buclizine is one of three drugs contained in Migraleve tablets, marketed ...

cyclizine Cyclizine, sold under a number of brand names, is a medication used to treat and prevent nausea, vomiting and dizziness due to motion sickness or vertigo. It may also be used for nausea after general anaesthesia or that which developed from opio ...

, and

hydroxyzine Hydroxyzine, sold under the brand names Atarax, Vistaril and 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 in ...

, but has a shorter

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...

of six hours compared to

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.Clinical Pharmacology
Clinical Pharmacology
revised 20 November 2009, accessed 7 November 2010. Meclizine is sometimes combined with opioids, especially ones of the open-chain class like

methadone Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...

dextropropoxyphene Dextropropoxyphene is an analgesic in the opioid category, patented in 1955 and manufactured by Eli Lilly and Company. It is an optical isomer of levopropoxyphene. It is intended to treat mild pain and also has antitussive (cough suppressant) a ...

, and

dipipanone Dipipanone (Pipadone) is a strong opioid analgesic drug, used for acute pain by mouth (PO) for adults - initially 10 mg every 6 hours, then increased if necessary up to 30 mg every 6 hours, with the dose to be increased gradually. It is often use ...

. Similarly, Diconal is a combination drug containing dipipanone and

Synthesis

(4-Chlorphenyl)-phenylmethanol is halogenated with

thionyl chloride Thionyl chloride is an inorganic compound with the chemical formula . It is a moderately volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a chlorinating reagent, with approximately per year bein ...

before adding acetylpiperazine. The acetyl group is cleaved with diluted

sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular formu ...

. An N-alkylation of the piperazine ring with 3-methylbenzylchloride completes the synthesis. Meclozine synthesis 01

Alternatively, the last step can be replaced by a reductive N-alkylation with 3-methylbenzaldehyde. The reductive agent is

hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic, an ...

, and Raney nickel is used as a

catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

Meclizine is obtained and used as a

racemate In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

, a 1:1 mixture of the two

stereoisomer In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...

s. Drug forms contain the racemic dihydrochloride.

Names

Meclizine is an international nonproprietary name. 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 Pyridoxine, is a form of vitamin B6 found commonly in food and used as a dietary supplement. As a supplement it is used to treat and prevent pyridoxine deficiency, sideroblastic anaemia, pyridoxine-dependent epilepsy, certain metabolic disorde ...

(2/3). In Canada, Antivert Tab (which is no longer available) was a combination of meclizine and

nicotinic acid Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...

.DrugBank
Drugbank: Drug card for Meclizine
David Wishard: University of Alberta, Canada. Accessed 7 November 2010.

Notes

References

External links

* * {{Portal bar , Medicine Antiemetics Chlorcyclizines Motion sickness Pregnane X receptor agonists Wikipedia medicine articles ready to translate 3-Tolyl compounds