Meclozine
Encyclopedia
Meclozine is an antihistamine
considered to be an antiemetic
. It is sold under the brand names Bonine, Bonamine, Antivert, Postafen, Sea Legs, and Dramamine (Less Drowsy Formulation). Emesafene is a combination of meclozine (1/3) and pyridoxine
(2/3). In Canada, Antivert Tab (which is no longer available) was a combination of meclozine and nicotinic acid.
class. Meclozine is structurally and pharmacologically similar to buclizine
, cyclizine
, and hydroxyzine
, but has a shorter half-life
of 6 hours compared to cyclizine and hydroxyzine with about 20 hours. It is used as an antivertigo/antiemetic agent, specifically in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness.
, 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
.
(FDA) to treat symptoms of motion sickness
and for management of vertigo
that stems from diseases affecting the vestibular system
. Meclozine's safety and efficacy in children younger than 12 years old has not been established, therefore use in this population is not recommended. Also, meclozine should be taken with caution in the elderly (older than 65 years) because of increased risk of confusion and amnesia.
, such as nausea, vomiting, and dizziness. The recommended dose is 25–50 mg orally, taken 1 hour before travel. The dose may be repeated every 24 hours as needed.
The drug is also safe for treating nausea in pregnancy
and is a first-line therapy for this use. Doxylamine
is similarly safe.
experienced as a result of inner ear infections or other conditions. The recommended dose is 25–100 mg per day orally, separated into divided doses.
. A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling, severe dizziness, and/or trouble breathing.
agent, meclozine 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 meclozine to the elderly.
before adding acetylpiperazine. The acetyl group is cleaved with diluted sulfuric acid
. An N-alkylation of the piperzine ring with 3-methylbenzylchloride completes the synthesis.
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.
Meclozine is obtained and used as a racemate, a 1:1 mixture of the two stereoisomers. Drug forms contain the dihydrochloride.
Antihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
considered to be an antiemetic
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....
. It is sold under the brand names Bonine, Bonamine, Antivert, Postafen, Sea Legs, and Dramamine (Less Drowsy Formulation). Emesafene is a combination of meclozine (1/3) and pyridoxine
Pyridoxine
Pyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. It is often used as 'pyridoxine hydrochloride'.-Chemistry:...
(2/3). In Canada, Antivert Tab (which is no longer available) was a combination of meclozine and nicotinic acid.
Classification
Meclozine is a first-generation antihistamine of the piperazinePiperazine
Piperazine is an organic compound that consists of a six-membered ring containing two opposing nitrogen atoms. Piperazine exists as small alkaline deliquescent crystals with a saline taste....
class. Meclozine is structurally and pharmacologically similar to buclizine
Buclizine
Buclizine is an antihistamine and anticholinergic of the piperazine derivative family. It is considered to be an antiemetic, similar to meclozine....
, cyclizine
Cyclizine
Cyclizine is an antihistamine drug used to treat nausea, vomiting and dizziness associated with motion sickness, vertigo and post-operatively following administration of general anaesthesia and opioids.-Indications:...
, and hydroxyzine
Hydroxyzine
Hydroxyzine is a first-generation antihistamine of the diphenylmethane and piperazine classes. It was first synthesized by Union Chimique Belge in 1956 and was marketed by Pfizer in the United States later the same year, and is still in widespread use today....
, but has a shorter half-life
Biological half-life
The biological half-life or elimination half-life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH definition...
of 6 hours compared to cyclizine and hydroxyzine with about 20 hours. It is used as an antivertigo/antiemetic agent, specifically in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness.
Mechanism of action
Meclozine is an antagonist at H1 receptors. It possesses anticholinergicAnticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
, central nervous system depressant, and local anesthetic effects. Its antiemetic
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....
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
Chemoreceptor trigger zone
The chemoreceptor trigger zone , is an area of the medulla that receives inputs from blood-borne drugs or hormones, and communicates with the vomiting center, to initiate vomiting. The CTZ is close to the area postrema on the floor of the fourth ventricle and is outside of the blood-brain barrier...
.
Uses
Meclozine is approved by the U.S. Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) to treat symptoms of motion sickness
Motion sickness
Motion sickness or kinetosis, also known as travel sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...
and for management of vertigo
Vertigo
Vertigo is a form of dizziness.Vertigo may also refer to:* Vertigo , a 1958 film by Alfred Hitchcock**Vertigo , its soundtrack** Vertigo effect, or Dolly zoom, a special effect in film, named after the movie...
that stems from diseases affecting the vestibular system
Vestibular system
The vestibular system, which contributes to balance in most mammals and to the sense of spatial orientation, is the sensory system that provides the leading contribution about movement and sense of balance. Together with the cochlea, a part of the auditory system, it constitutes the labyrinth of...
. Meclozine's safety and efficacy in children younger than 12 years old has not been established, therefore use in this population is not recommended. Also, meclozine should be taken with caution in the elderly (older than 65 years) because of increased risk of confusion and amnesia.
Motion sickness
Meclozine is effective in inhibiting the symptoms of motion sicknessMotion sickness
Motion sickness or kinetosis, also known as travel sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...
, such as nausea, vomiting, and dizziness. The recommended dose is 25–50 mg orally, taken 1 hour before travel. The dose may be repeated every 24 hours as needed.
The drug is also safe for treating nausea in pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
and is a first-line therapy for this use. Doxylamine
Doxylamine
Doxylamine is one of the many sedating antihistamines used by itself as a short-term sedative, and in combination with other drugs as a night-time cold and allergy relief drug...
is similarly safe.
Vertigo
Meclozine may be effective in relieving vertigoVertigo
Vertigo is a form of dizziness.Vertigo may also refer to:* Vertigo , a 1958 film by Alfred Hitchcock**Vertigo , its soundtrack** Vertigo effect, or Dolly zoom, a special effect in film, named after the movie...
experienced as a result of inner ear infections or other conditions. The recommended dose is 25–100 mg per day orally, separated into divided doses.
Side effects
Some common side effects such as drowsiness, dry mouth, and tiredness may occur. Meclozine has been shown to have fewer dry mouth side effects than the traditional treatment for motion sickness, transdermal scopolamineScopolamine
Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae family of plants, such as henbane, jimson weed and Angel's Trumpets , and corkwood...
. A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling, severe dizziness, and/or trouble breathing.
Drowsiness
Drowsiness may result as a side effect of taking meclozine. Users are advised not to operate heavy machinery while under the influence. The consumption of alcohol while under the influence of meclozine may result in additional drowsiness.Special considerations in the elderly
As with any anticholinergicAnticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
agent, meclozine may cause confusion or aggravate symptoms in those with dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
in the geriatric population (older than 65 years). Therefore caution should be used when administering meclozine to the elderly.
Synthesis
(4-Chlorphenyl)-phenylmethanol is halogenated with thionyl chlorideThionyl chloride
Thionyl chloride is an inorganic compound with the formula SOCl2. It is a reactive chemical reagent used in chlorination reactions. It is a colorless, distillable liquid at room temperature and pressure that decomposes above 140 °C. Thionyl chloride is sometimes confused with sulfuryl...
before adding acetylpiperazine. The acetyl group is cleaved with diluted sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
. An N-alkylation of the piperzine ring with 3-methylbenzylchloride completes the synthesis.
Alternatively, the last step can be replaced by a reductive N-alkylation with 3-methylbenzaldehyde. The reductive agent is hydrogen
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
, and Raney nickel
Raney nickel
Raney nickel is a solid catalyst composed of fine grains of a nickel-aluminium alloy, used in many industrial processes. It was developed in 1926 by American]] engineer Murray Raney as an alternative catalyst for the hydrogenation of vegetable oils in industrial processes...
is used as a catalyst.
Meclozine is obtained and used as a racemate, a 1:1 mixture of the two stereoisomers. Drug forms contain the dihydrochloride.