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
Well absorbed after oral administration. /Antihistamines, phenothiazine-derivative/
The H1 antagonists are well absorbed from the GI tract. Following oral administration, peak plasma concn are achieved in 2 to 3 hr and effects usually last 4 to 6 hr; however, some of the drugs are much longer acting ... . /Histamine Antagonists: H1 Antagonists/
... H1 antagonists are eliminated more rapidly by children than by adults and more slowly in those with severe liver disease. /Histamine Antagonists: H1 Antagonists/

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Metabolism / Metabolites
MAIN SITE OF METABOLIC TRANSFORMATION IS LIVER. /ANTIHISTAMINES/
H1 blockers are among the many drugs that induce hepatic microsomal enzymes, and they may facilitate their own metabolism. /Histamine Antagonists: H1 Antagonists/

Interactions
METHDILAZINE HYDROCHLORIDE (3 MG/KG IP) POTENTIATED THE PENTOBARBITONE INDUCED HYPNOSIS IN RATS.
Concurrent use /with alcohol or other CNS depression-producing medications/ may potentiate the CNS depressant effects of either these medications or antihistamines; also, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications. /Antihistamines, phenothiazine-derivative/
Concurrent use /with amphetamines/ may decrease stimulant effects of amphetamines since phenothiazine derivatives produce alpha-adrenergic blockage. /Antihistamines, phenothiazine-derivative/
Anticholinergic effects may be potentiated when /anticholinergics or other medications with anticholinergic activity/ are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy. /Antihistamines, phenothiazine-derivative/
For more Interactions (Complete) data for METHDILAZINE HYDROCHLORIDE (21 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.

Methdilazine hydrochloride is a white microcrystalline powder with a slight odor. pH (1% aqueous solution) 4.8-6. (NTP, 1992)
Methdilazine hydrochloride is the hydrochloride salt of methdilazine. It contains a methdilazine.
See also: Methdilazine (has active moiety).

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Mechanism of Action
Antihistamines used in the treatment of allergy act by competing with histamine for H1-receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus. In addition, the anticholinergic actions of most antihistamines provide a drying effect on the nasal and oral mucosa. /Antihistamines, phenothiazine-derivative/
H1 antagonists inhibit most responses of smooth muscle to histamine. Antagonism of the constrictor action of histamine on respiratory smooth muscle is easily shown in vivo and in vitro. /Histamine Antagonists: H1 Antagonists/
H1 antagonists strongly block the action of histamine that results in increased permeability and formation of edema and wheal. /Histamine Antagonists: H1 Antagonists/
Within the vascular tree, the H1 antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects that are mediated by H1 receptors on endothelial cells. Residual vasodilatation reflects the involvement of H2 receptors on smooth muscle and can be suppressed only by the concurrent administration of an H2 antagonist. Effects of the histamine antagonists on histamine-induced changes in systemic blood pressure parallel these vascular effects. /Histamine Antagonists: H1 Antagonists/
Many of the H1 antagonists tend to inhibit responses to acetylcholine that are mediated by muscarinic receptors. These atropine-like actions are sufficiently prominent in some of the drugs to be manifest during clinical usage ... . /Histamine Antagonists: H1 Antagonists/

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Therapeutic Uses
Histamine H1 Antagonists
A PHENOTHIAZINE ANTIHISTAMINIC EFFECTIVE FOR THE SYMPTOMATIC RELIEF OF URTICARIA. IT HAS ALSO BEEN USED FOR THE THERAPY OF MIGRAINE HEADACHE.
Antihistamines are indicated in the symptomatic treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis due to inhalant allergens and foods. /Antihistamines, phenothiazine-derivative; Included in US product labeling/
Antihistamines are indicated for the symptomatic treatment of pruritus associated with allergic reactions and of mild, uncomplicated allergic skin manifestations of urticaria and angioedema, in dermatographism, and in urticaria associated with transfusions. Methdilazine is also indicated in the treatment of pruritus associated with pityriasis rosea. /Antihistamines, phenothiazine-derivative; Included in US product labeling/
For more Therapeutic Uses (Complete) data for METHDILAZINE HYDROCHLORIDE (7 total), please visit the HSDB record page.

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Drug Warnings
IT SHOULD NOT BE GIVEN CONCOMITANTLY WITH OTHER PHENOTHIAZINES, ANTIHISTAMINES, OR MAO INHIBITORS.
IT IS CONTRAINDICATED IN ASTHMA, NARROW-ANGLE GLAUCOMA, AND NEWBORN INFANTS; ALSO IN ACUTELY ILL OR DEHYDRATED CHILDREN, BECAUSE OF THE GREATER SUSCEPTIBILITY TO DYSTONIAS WITH PHENOTHIAZINES.
Phenothiazines have been reported to cause jaundice and extrapyramidal symptoms in infants whose mothers received these medications during pregnancy. /Antihistamines, phenothiazine-derivative/
Small amounts of antihistamines may be distributed into breast milk; use is not recommended in nursing mothers because of the risk of adverse effects, such as unusual excitement or irritability, in infants. Antihistamines may inhibit lactation because of their anticholinergic actions. /Antihistamines, phenothiazine-derivative/
For more Drug Warnings (Complete) data for METHDILAZINE HYDROCHLORIDE (18 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.)