The inhibitory effect of mediizine hydrochloride (about 0–20 μg/mL, 18 h) ranges from 5 μg/mL to 15 μg/mL on a variety of mycobacteria[1].

In H37Rv-infected mice, mediazine hydrochloride (10 μg/gm body weight/day, intraperitoneal injection) exerts an antagonistic effect on mycobacteria [1]. Mice infected with Mycobacterium tuberculosis (Mtb) H37Rv may have a higher survival rate when given medizizine hydrochloride (10 mg/kg daily for 28 days) [2].

Cell proliferation experiment [1]
Cell Types: M. smegmatis 798/1546, M., fortuitum 1529, M. scrofulaceum 1323, M. gordonae 1324, M. rnarinum 50, M., flavescens 1541, M. terrae 1450, M. terrae 1450, M. terrae 1450. Tuberculosis, H37Ra 16, H37Rv 16, K1, K2, ICRC bacilli, Bacillus 'skinnis'.
Tested Concentrations: Approximately 0-20 μg/mL
Incubation Duration: 18 hrs (hours)
Experimental Results: Inhibition of mycobacteria with MIC values ranging from 5 μg/mL to 15 μg/mL.

Animal/Disease Models: H37Rv infected mice [1]
Doses: 10 μg/gm body weight/day, 6 weeks
Route of Administration: intraperitoneal (ip) injection
Experimental Results: Demonstrated antimycobacterial activity against mycobacteria.

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Animal/Disease Models: Swiss albino male mice infected with Mycobacterium tuberculosis (Mtb) H37Rv [2]
Doses: 10 mg/kg per day for 28 days
Route of Administration: Oral
Experimental Results: Survival time extended to 28 days, no signs of disease, The survival rate is 71.42%.

Absorption, Distribution and Excretion
Absorption is good after oral administration. /Antichrists, phenothiazine derivatives/
H1 receptor antagonists are well absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 2 to 3 hours after oral administration, and the effect usually lasts for 4 to 6 hours; however, some drugs have a longer duration of action… /Histamine antagonists: H1 receptor antagonists/
…H1 receptor antagonists are cleared faster in children than in adults, while clearance is slower in patients with severe liver disease. /Histamine antagonists: H1 receptor antagonists/
Metabolism/Metabolites

The primary site of metabolic transformation is the liver. /Antichrists/
H1 receptor blockers are among many drugs that can induce hepatic microsomal enzymes, which may promote their own metabolism. Histamine antagonists: H1 receptor antagonists

Interactions
Metoprazine hydrochloride (3 mg/kg, intraperitoneal injection) enhances pentobarbital-induced hypnosis in rats. Concomitant use with alcohol or other central nervous system depressants may enhance the central nervous system depressant effects of these drugs or antihistamines; furthermore, concomitant use with maprotiline or tricyclic antidepressants may enhance the antihistamine or anticholinergic effects of these drugs. (Antihistamines, phenothiazine derivatives) Concomitant use with amphetamine may reduce the excitatory effect of amphetamine because phenothiazine derivatives block α-adrenergic receptors. /Phenothiazine antihistamines/ When anticholinergic drugs or other drugs with anticholinergic activity are used concomitantly with antihistamines, the anticholinergic effect may be enhanced; patients should be advised to report gastrointestinal problems promptly, as concomitant use may lead to paralytic ileus. /Phenothiazine antihistamines/
For more complete data on drug interactions of metoprazine hydrochloride (21 in total), please visit the HSDB record page.

[1]. Antimycobacterial activity of methdilazine (Md), an antimicrobic phenothiazine. APMIS. 1993 Jun;101(6):449-54.

[2]. Activity of the phenothiazine methdilazine alone or in combination with isoniazid or streptomycin against Mycobacterium tuberculosis in mice. J Med Microbiol. 2009 Dec;58(Pt 12):1667-1668.

Mederapazine hydrochloride is a white microcrystalline powder with a slight odor. The pH (1% aqueous solution) is 4.8–6. (NTP, 1992)
Mederapazine hydrochloride is the hydrochloride salt of mederapazine. It contains mederapazine.
See also: Mederapazine (with active moiety).
Mechanism of Action
Antihistamines used to treat allergies act by competing with histamine for H1 receptor sites on effector cells. They can prevent (but cannot reverse) reactions mediated solely by histamine. Antihistamines antagonize most of the pharmacological effects of histamine to varying degrees, including urticaria and pruritus. In addition, the anticholinergic effects of most antihistamines can cause dryness of the nasal and oral mucosa. /Antihistamines, phenothiazine derivatives/
H1 receptor antagonists inhibit most of the smooth muscle response to histamine. The antagonistic effect of H1 receptor antagonists on the contractile effect of histamine on respiratory smooth muscle is readily confirmed in vivo and in vitro experiments. /Histamine Antagonists: H1 Receptor Antagonists/
H1 receptor antagonists potently block the effects of histamine, thereby inhibiting increased vascular permeability and the formation of edema and wheals. /Histamine Antagonists: H1 Receptor Antagonists/
In the vascular system, H1 receptor antagonists inhibit both the vasoconstrictive effects of histamine and, to some extent, the more rapid vasodilation mediated by H1 receptors on endothelial cells. Residual vasodilation reflects the involvement of H2 receptors on smooth muscle and can only be inhibited by concurrent administration of H2 receptor antagonists. The effects of histamine antagonists on histamine-induced systemic blood pressure changes parallel these vascular effects. /Histamine Antagonists: H1 Receptor Antagonists/
Many H1 receptor antagonists tend to inhibit acetylcholine responses mediated by muscarinic receptors. These atropine-like activities are so pronounced in some drugs that they can be observed in clinical applications… /Histamine Antagonists: H1 Receptor Antagonists/

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Therapeutic Uses
Histamine H1 Receptor Antagonists
A phenothiazine antihistamine, effective in relieving urticaria symptoms. It has also been used to treat migraines.
Antihistamines are indicated for the treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis caused by inhaled allergens and foods. /Antihistamines, phenothiazine derivatives; included in the US product label/
Antihistamines are indicated for the treatment of itching associated with allergic reactions and symptoms of mild, uncomplicated allergic skin manifestations such as urticaria and angioedema, dermatographia, and transfusion-related urticaria. Metoprazine is also indicated for the treatment of itching associated with pityriasis rosea. /Antihistamines, phenothiazine derivatives; included in the US product label/
For more complete data on the therapeutic uses of metoprazine hydrochloride (7 types), please visit the HSDB record page.

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Drug Warnings
This product should not be taken concurrently with other phenothiazines, antihistamines, or monoamine oxidase inhibitors.
This product is contraindicated in children with asthma, narrow-angle glaucoma, and newborns; it is also contraindicated in children with acute illness or dehydration, as these children are more prone to dystonia when used in combination with phenothiazines.
It has been reported that maternal use of phenothiazines during pregnancy can cause jaundice and extrapyramidal symptoms in infants. /Phenothiazines Antihistamines/
Small amounts of antihistamines may pass into breast milk; therefore, use is not recommended for breastfeeding women due to the potential adverse effects on infants, such as abnormal excitement or irritability. Antihistamines may inhibit lactation due to their anticholinergic effects. /Phenothiazines Antihistamines/
For more complete data on drug warnings for metoprazine hydrochloride (18 in total), please visit the HSDB record page.

C18H20N2S.HCL

332.89074

332.111

1229-35-2

Methdilazine;1982-37-2

14676

White to off-white solid powder

430.4ºC at 760mmHg

187.5-189ºC

214.1ºC

1.3E-07mmHg at 25°C

1.642

5.045

1

3

2

22

339

0

IEISBKIVLDXSMZ-UHFFFAOYSA-N

InChI=1S/C18H20N2S.ClH/c1-19-11-10-14(12-19)13-20-15-6-2-4-8-17(15)21-18-9-5-3-7-16(18)20;/h2-9,14H,10-13H2,1H3;1H

10-[(1-methylpyrrolidin-3-yl)methyl]phenothiazine;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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.)