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 receptor antagonists are reported to be readily absorbed after oral administration. After oral administration, meclopramide reaches peak plasma concentration (Cmax) approximately 3 hours later, ranging from 1.5 to 6 hours. Meclopramide is excreted in the urine as metabolites and in the feces unchanged. The volume of distribution of meclopramide in humans has not been fully studied. Some studies suggest that meclopramide may be secreted into breast milk. Data on the clearance of meclopramide are limited. Benzo[a]hydroxypiperazine and its N-dealkylated products are distributed in all tissues of rats and can be transferred to the fetus. This drug is excreted in the feces unchanged and in the urine as norchlorocyclorhizine. /Meclopramide Hydrochloride/

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Metabolic/Metabolic Products Limited data are available on the metabolism of meclopramide in humans. Based on in vitro studies, meclopramide may undergo aromatic hydroxylation or benzyl oxidation catalyzed by the hepatic CYP2D6 enzyme. Oxidative dealkylation is the main metabolic pathway for benzo[a]hydroxypiperazine drugs… norchlorcyclorhizine is… the main metabolite of meclopramide. The metabolic pathway of meclopramide in humans is not yet clear. In rats, meclopramide is metabolized (possibly in the liver) to norchlorcyclorhizine. This metabolite is distributed in most body tissues and can cross the placenta. Liver. Half-life: 6 hours. The plasma elimination half-life of meclopramide hydrochloride in humans is approximately 5-6 hours. The plasma half-life of this drug is 6 hours. /Meclopramide Hydrochloride/

Toxicity Summary
Meclopramide, in addition to its function as an H1 receptor antagonist, also possesses anticholinergic, central nervous system depressant, and local anesthetic effects. Meclopramide can inhibit labyrinthine excitability and vestibular stimulation, and may affect the medullary chemoreceptor trigger zone. Toxicity Data
LD50: 1600 mg/kg (oral) (A701) LD50: 659 mg/kg (intraperitoneal) (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

Antihistamine; Antiemetic; H1 Histamine Receptor Antagonist
A long-acting antihistamine effective in preventing or treating nausea, vomiting, and dizziness caused by motion sickness. …The effect lasts 9–24 hours after a single dose. /Mecclorazine Hydrochloride/
...H1 receptor antagonists, particularly dimenhydrinate and mecclorazine, are generally beneficial for vestibular dysfunction (e.g., Meniere's disease) and other types of true vertigo.
...A large drug surveillance program has not identified any birth defects in the clinically used dose range.
For more complete data on the therapeutic uses of mecclorazine (10 in total), please visit the HSDB record page.

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Drug Warnings
Pediatric dosage has not been determined.
A woman with cirrhosis who died in a coma had extrapyramidal disease prior to taking one tablet of aceclorazine daily for four consecutive days. (Mecclorazine hydrochloride 25 mg and pyridoxine 50 mg) For patients with chronic liver disease, extra caution must be exercised when prescribing medications metabolized by the liver. ...Meclizine hydrochloride may impair a patient's ability to perform dangerous activities requiring mental alertness or physical coordination (e.g., operating machinery or driving...). Furthermore, when antihistamines such as meclizine hydrochloride are taken concomitantly with other central nervous system depressants (including barbiturates, sedatives, and alcohol), an additive effect of central nervous system depression may occur. If meclizine hydrochloride is used concomitantly with other depressants, caution should be exercised to avoid overdose. The anticholinergic effects of meclizine hydrochloride should be considered in patients with angle-closure glaucoma or benign prostatic hyperplasia. Meclizine is contraindicated in patients with known hypersensitivity to it. The safety and efficacy of meclizine in children under 12 years of age have not been established; therefore, its use is not recommended. Meclizine has been shown to be teratogenic in animals. Although retrospective human studies have shown that use of meclizine during pregnancy may not be associated with teratogenicity, the manufacturer states that this medication is contraindicated in pregnant women or women who may become pregnant.

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Pharmacodynamics
Mectin acts on the higher centers of the brain to relieve nausea, vomiting, or dizziness. It is effective for nausea and vomiting from a variety of causes, including motion sickness and diseases affecting the vestibular system. Mecclozine has an onset of action of approximately 1 hour and its effects last for 8 to 24 hours. It has been reported that mecclozine can cause drowsiness due to its anticholinergic effects.

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.)