H1 Receptor; antihistamine

Meclizine (Meclozine; 50 µM; 24 hours) reportedly inhibits apoptosis in STHdh cells, as seen by the considerable increase in cell survival 24 hours after serum withdrawal (based on caspase 3 and 7 cleavage). With an EC50 of 17.3 µm, the rescue effect was dose-dependent. When comparing the highest efficacy to the vehicle, the survival rate increased by 218%. Meclizine prevents serum withdrawal-induced apoptosis in striatal cells expressing polyglutamine (polyQ)-amplified huntingtin in both mutant (STHdhQ111/111) and wild-type (STHdhQ7/7) striatal cells [2].

Mice protected against renal ischemia by meclizine (Meclozine; 10-100 mg/kg; ip). It was demonstrated that pretreatment of mice's kidneys with 100 mg/kg Meclizine 17 or 24 hours prior to ischemia had a protective effect. Meclizine increases glycolysis and directly inhibits the Kennedy route of phosphatidylethanolamine production to lower mitochondrial oxygen consumption [4].

Cell Viability Assay[2]
Cell Types: Mouse striatal cells expressing wild-type (STHdhQ7/7) or mutant (STHdhQ111/111) huntingtin
Tested Concentrations: 50 µM
Incubation Duration: 24 hrs (hours)
Experimental Results: Cells in STHdhQ111/111 Survival rates were Dramatically increased for cells 24 hrs (hours) after removal of serum.

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Western Blot Analysis[2]
Cell Types: mutant (STHdhQ111/111) and wild type (STHdhQ7/7) Striatal cell
Tested Concentrations: 50 µM
Incubation Duration: 0, 4, 10, 24 hrs (hours)
Experimental Results: Inhibition of apoptosis ( Based on caspase 3) and 7 cleavage.

Animal/Disease Models: 8-10 weeks old male C57BL/6 mice [4]
Doses: 10, 30, 60 or 100 mg/kg
Route of Administration: intraperitonealadministration
Experimental Results: Protect mice from renal ischemia-reperfusion injury .

Absorption, Distribution and Excretion
Most histamine H1 antagonists are reported to be readily absorbed following oral administration. Upon oral administration, the time to reach peak plasma concentrations (Cmax) of meclizine is about 3 hours post-dose, with the value ranging from 1.5 to 6 hours.
Meclizine is excreted in the urine as metabolites and in the feces as unchanged drug.
The volume of distribution of meclizine in humans has not been fully studied. It is proposed that meclizine may be excreted into breast milk.
There is limited data on the clearance of meclizine.
BENZHYDROLPIPERAZINES & THEIR N-DEALKYLATION PRODUCTS ARE DISTRIBUTED IN ALL TISSUES OF RATS & TRANSFERRED TO FETUS.
The drug is excreted in feces unchanged and in urine as norchlorcyclizine. /Meclizine hydrochloride/

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Metabolism / Metabolites
There is limited human data on meclizine metabolism. According to the findings of _in vitro_ studies, meclizine may undergo aromatic hydroxylation or benzylic oxidation mediated by the hepatic CYP2D6 enzyme.
OXIDATIVE N-DEALKYLATION IS MAIN METAB PATHWAY OF BENZHYDROLPIPERAZINES... NORCHLORCYCLIZINE IS...MAJOR METABOLITE OF MECLIZINE.
The metabolic fate of meclizine in humans in unknown. In rats, meclizine is metabolized (probably in the liver) to norchlorcyclizine. This metabolite is distributed throughout most body tissues and crosses the placenta.
Hepatic
Half Life: 6 hours

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Biological Half-Life
Meclizine has a plasma elimination half-life of about 5-6 hours in humans.
The drug has a plasma half-life of 6 hr. /Meclizine hydrochloride/

Toxicity Summary
Along with its actions as an antagonist at H₁-receptors, meclizine also possesses anticholinergic, central nervous system depressant, and local anesthetic effects. Meclizine depresses labyrinth excitability and vestibular stimulation and may affect the medullary chemoreceptor trigger zone.

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Toxicity Data
LD50: 1600 mg/kg (oral) (A701)
LD50: 659 mg/kg (i.p.) (A701)

[1]. Safety and Efficacy in the Treatment and Prevention of Motion Sickness.

[2]. Meclizine is neuroprotective in models of Huntington's disease. Hum Mol Genet. 2011 Jan 15;20(2):294-300.

[3]. Meclizine Is an Agonist Ligand for Mouse Constitutive Androstane Receptor (CAR) and an Inverse Agonist for Human CAR.

[4]. Meclizine Preconditioning Protects the Kidney Against Ischemia-Reperfusion Injury. EBioMedicine. 2015 Jul 29;2(9):1090-101.

Therapeutic Uses
Anti-Allergic Agents; Antiemetics; Histamine H1 Antagonists
A LONG-ACTING ANTIHISTAMINIC AGENT WHICH IS EFFECTIVE IN PREVENTION OR TREATMENT OF NAUSEA, VOMITING & DIZZINESS ASSOC WITH MOTION SICKNESS. ... ACTION OF SINGLE DOSE PERSISTS FOR 9-24 HR. /MECLIZINE HYDROCHLORIDE/
... H1 antagonists, notably dimenhydrinate and meclizine, are often of benefit in vestibular disturbances, such as Meniere's disease, and in other types of true vertigo.
...LARGE DRUG SURVEILLANCE PROGRAMS HAVE NOT DEMONSTRATED BIRTH DEFECTS CLINICALLY IN DOSAGE RANGES EMPLOYED.
For more Therapeutic Uses (Complete) data for MECLIZINE (10 total), please visit the HSDB record page.

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Drug Warnings
CHILDREN DOSAGE HAS NOT BEEN ESTABLISHED.
WOMAN WITH CIRRHOSIS HAD EXTRAPYRAMIDAL DISORDERS PRIOR TO DEATH IN COMA, FOLLOWING 1 TABLET/DAY FOR 4 DAYS OF ANCOLOXIN (MECLIZINE 25 MG & PYRIDOXINE 50 MG). EXTREME CAUTION IS EMPHASIZED IN PRESCRIBING DRUGS METAB IN LIVER TO PT WITH CHRONIC LIVER DISEASE.
... Meclizine may impair their ability to perform hazardous activities requiring mental alertness or physical coordination (e.g., operating machinery or driving ... ). In addition, additive CNS depression may occur when antihistamines, such as meclizine, are admin concomitantly with other CNS depressants including barbiturates, tranquilizers, and alcohol. If meclizine is used concomitantly with other depressant drugs, caution should be used to avoid overdosage. The anticholinergic effects of the drug should be considered when admin meclizine to patients with angle-closure glaucoma or prostatic hypertrophy. Meclizine is contraindicated in patients who are hypersensitive to it.
Safety and efficacy of meclizine in children younger than 12 yr of age have not been established; therefore ... use ... is not recommended.
Meclizine is teratogenic in animals. Although retrospective studies in humans suggest that the use of meclizine during pregnancy is probably not assoc with teratogenic effects, the manufacturers state that the drug is contraindicated in women who are or may become pregnant.

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Pharmacodynamics
Meclizine works on the higher centres of the brain to reduce nausea, vomiting, or vertigo. It is effective against nausea and vomiting arising from many causes, including motion sickness and disorders affecting the vestibular system. The onset of action of meclizine is about 1 hour, with effects lasting between 8 to 24 hours. Meclizine is reported to cause drowsiness due to its anticholinergic actions.

C25H27N2CL

390.94828

426.163

C, 76.81; H, 6.96; Cl, 9.07; N, 7.17

569-65-3

Meclizine dihydrochloride;1104-22-9;Meclizine-d8 dihydrochloride;1432062-16-2;Meclizine dihydrochloride monohydrate;31884-77-2

4034

Typically exists as solid at room temperature

1.159 g/cm3

1.5 g/100 mL (25ºC)

153-157ºC

253.3ºC

6.233

0

2

5

28

448

0

CC1=CC(=CC=C1)CN2CCN(CC2)C(C3=CC=CC=C3)C4=CC=C(C=C4)Cl

OCJYIGYOJCODJL-UHFFFAOYSA-N

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

1-[(4-chlorophenyl)-phenylmethyl]-4-[(3-methylphenyl)methyl]piperazine

meclizine; Meclozine; 569-65-3; HSDB3113; HSDB-3113; HSDB 3113; Parachloramine; Bonadettes; Histamethine; Histamethizine; Histametizine;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)