Mesoridazine inhibits human ether-a-go-go related gene (HERG) currents in a concentration-dependent manner (IC50 = 550 nM, 0 mV). The blocking action increases dramatically along the voltage range where HERG activation occurs, leading to maximal Saturable channel activity when HERG voltage is reached [1]. The total absorption rates of 15.94 ± 4.04% and 39.24 ± 5.11% of mesoridazine (15 mM; 24 hours) in nude mouse and pig skin, respectively, were reported [3].

Mesoridazine (15 mM) shows strong action and persistent analgesia in preventing cutaneous discomfort when applied topically once or once a day for seven days [3]. Mice in the nude were given a topical application of mesoridazine (15 mM) for six hours. The intradermal concentration of the drug was 0.34 - 0.74 nmol/mg [3].

Animal/Disease Models: 8weeks old female nude mice [3]
Doses: 15 mM
Route of Administration: Topical administration, once (analgesic test) or one time/day for 7 days (stimulation test)
Experimental Results:Shows analgesic effect. A slight increase in transepidermal water loss (TEWL) from 7.8 to 9.9 g/m2/h was observed.

Absorption, Distribution and Excretion
Absorbed well in the gastrointestinal tract. In monkeys (10-day cycle), the total urinary and fecal excretion rate of thioridazine is 64-76%, and that of mesolidazine is 83-92% (2-4 times higher in feces). The higher excretion rate of the latter may be due to lower overall tissue absorption or less extensive enterohepatic circulation. Absorbed well in the gastrointestinal tract. Onset of action, duration of action, and metabolic pathways… have not been precisely determined (human, oral, intramuscular). Animal studies indicate that approximately 2/3 of the dose is excreted in feces via bile, and 1/3 in urine. Phenothiazines can cross the placental barrier and may be present in the breast milk of lactating women. Phenothiazines and their metabolites are excreted in urine, bile, and feces. Some metabolites and free drug may be detected in urine up to 6 months after discontinuation. /Human, Oral, Intramuscular/
Phenothiazines are well absorbed from the gastrointestinal and parenteral routes. Generally…cleared from plasma within about 3 hours…distributed to most body tissues…high drug concentrations remain unchanged…in the brain…metabolites are mainly found in the lungs, liver, kidneys…spleen /Human, Oral, Intramuscular/
Metabolism/Metabolites

Thioridazine-2-sulfoxide may be converted to thioridazine-2,5-disulfoxide in rats: ZEHNDER, K et al., BIOCHEM PHARMAC, 11, 535 (1962). /Excerpt from Table/
Thioridazine-2-sulfoxide is a known metabolite of thioridazine in humans.
Half-life: 24 to 48 hours
Biological half-life

24 to 48 hours

Toxicity Summary
According to animal studies, mesophorazine, like other phenothiazines, acts indirectly on the reticular formation, thereby reducing neuronal activity entering the reticular formation without affecting its inherent ability to activate the cerebral cortex. Furthermore, phenothiazines exert their effects at least partially through inhibition of the hypothalamic center. From a neurochemical perspective, phenothiazines are believed to exert their therapeutic effects through central adrenergic blockade.

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Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Since there is no published experience regarding the use of mesophorazine during lactation, it is recommended to prioritize other antipsychotic medications. ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found. ◉ Effects on Lactation and Breast Milk Phenothiazines can cause galactorrhea in 26% to 40% of female patients. Hyperprolactinemia appears to be the cause of galactorrhea. Hyperprolactinemia is caused by the drug blocking dopamine in the tuberous-infundibulum pathway. Prolactin levels in established lactating mothers may not affect their lactation capacity. Protein binding rate: 4%. Toxicity data: Oral LD50 in mice and rats were 560 ± 62.5 mg/kg and 644 ± 48 mg/kg, respectively. Interactions: Chlorpromazine and other antipsychotics… may block the hypotensive effect of guanethidine. /Chlorpromazine/ While the interaction between chlorpromazine and amphetamines has not been documented, it may apply to other phenothiazine derivatives. Phenothiazine drugs: Oral pretreatment with mesorizine hydrochloride 3 mg/kg was more effective than thioridazine hydrochloride (6 mg/kg) in reducing D-amphetamine sulfate-induced canine behavior.
When probucol is used in combination with phenothiazines, QT interval prolongation may increase the risk of ventricular tachycardia. /Phenothiazines/
For more complete data on interactions of mesoridines (31 in total), please visit the HSDB record page.

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Non-human toxicity values
Mice intravenous LD50: 33 mg/kg /benzenesulfonate/
Mice subcutaneous LD50: 611 mg/kg /benzenesulfonate/
Mice oral LD50: 346 mg/kg /benzenesulfonate/

[1]. Mesoridazine: an open-channel blocker of human ether-a-go-go-related gene K+ channel. J Mol Cell Cardiol. 2004 Jan;36(1):151-60.

[2]. Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses. Clin Pharmacol Ther. 2007 Nov;82(5):548-54.

[3]. Topically applied mesoridazine exhibits the strongest cutaneous analgesia and minimized skin disruption among tricyclic antidepressants: The skin absorption assessment. Eur J Pharm Biopharm. 2016 Aug;105:59-68.

Mesoridazine is a phenothiazine compound with a methylsulfinyl group substituted at the 2-position (para-sulfonium) and a nitrogen atom substituted with a 2-(1-methylpiperidin-2-yl)ethyl group. It is a dopaminergic antagonist and a first-generation antipsychotic. It belongs to the phenothiazine, sulfoxide, and tertiary amine classes. Mesoridazine is a phenothiazine antipsychotic with similar effects to chlorpromazine. Mesoridazine is a phenothiazine compound. Mesoridazine has been reported to be detected in Phomopsis phaseoli, and relevant data are available. Mesoridazine is only present in individuals who have used or taken the drug. It is a phenothiazine antipsychotic with similar effects to chlorpromazine. [PubChem] Based on animal studies, Mesoridazine, like other phenothiazine drugs, acts indirectly on the reticular formation, thereby reducing neuronal activity input to the reticular formation without affecting its inherent ability to activate the cerebral cortex. Furthermore, phenothiazines exert their effects at least partially by inhibiting the hypothalamic center. From a neurochemical perspective, phenothiazines are believed to exert their therapeutic effects through central adrenergic blocking. One phenothiazine antipsychotic drug has similar effects to chlorpromazine. Indications: Used to treat schizophrenia, organic brain disease, alcoholism, and psychoneurosis. Mechanism of Action: Based on animal studies, mesorizine, like other phenothiazines, acts indirectly on the reticular formation, thereby reducing neuronal activity entering the reticular formation without affecting its inherent ability to activate the cerebral cortex. Furthermore, phenothiazines exert their effects at least partially by inhibiting the hypothalamic center. From a neurochemical perspective, phenothiazines are believed to exert their therapeutic effects through central adrenergic blocking. …The therapeutic effects and side effects of antipsychotic drugs may be related to the inhibition of dopamine-activated adenylate cyclase. /Phenothiazines/

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Therapeutic Uses
Anthopsychiatric drugs, phenothiazines; dopamine antagonists
Anthopsychiatric drugs have a high therapeutic index and extremely high safety. Furthermore, most phenothiazines have relatively flat dose-response curves, allowing for use over a wide dose range. …Side effects are usually extensions of the drug's multiple pharmacological effects… /Phenothiazines/
…Indications for the treatment of schizophrenia, organ brain diseases, alcohol withdrawal symptoms, and psychoneurosis. Clinical studies to date have shown that mesolidazine benzylsulfonate has a lower incidence of adverse reactions compared to other phenothiazines. /Benzylsulfonate/
Thioridazine and mesolidazine benzylsulfonate treatment for 8 weeks. Patients treated with thioridazine showed better efficacy than those treated with mesolidazine benzylsulfonate. The effect of chemotherapy on patients with schizophrenia has been considered.
For more complete data on the therapeutic uses of mesolidazine (6 in total), please visit the HSDB record page.

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Drug Warnings
Nervous tranquilizers…should be used with extreme caution. If used, they should be avoided in untreated epilepsy patients and patients who are withdrawing from central nervous system depressants (such as alcohol, barbiturates, or benzodiazepines). Most antipsychotics…are safe for use in epilepsy patients if the dose is gradually increased while maintaining anticonvulsant therapy. /Phenothiazines/
Phenothiazines suppress ejaculation but do not affect erection. /Phenothiazines/
All phenothiazines cause weight gain and increased appetite…1-3% of patients experience peripheral edema, possibly due to endocrine reasons. /Phenothiazines/
Antipsychotics are not addictive…however, a degree of physical dependence may occur, with discomfort and sleep difficulties appearing a few days after abrupt discontinuation. Tolerance to sedation usually develops within days or weeks. Tolerance can be confirmed in animal behavior and biochemical studies. /Antipsychotic Drugs/
For more complete data on drug warnings for mesolidazine (20 in total), please visit the HSDB record page.

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Pharmacodynamics
Mesolidazine is the benzylsulfonate salt of thioridazine and is a phenothiazine sedative. Laboratory animal pharmacological studies have shown that mesolidazine has a typical pharmacodynamic spectrum of a potent sedative. Like other sedatives, it inhibits spontaneous movement in mice, prolongs thiopental and hexobarbital sleep in mice, and produces spindle waves and arousal blockade on electroencephalograms in rabbits. It effectively blocks the spinotomy reflex and antagonizes the excitatory and toxic effects of dextroamphetamine in mice. In vitro and in vivo studies have shown moderate adrenergic blocking activity, and in vivo studies have shown that it antagonizes serotonin. Intravenous injection can lower blood pressure in anesthetized dogs. In vitro studies have shown a weak anticholinergic effect.

C21H26N2OS2

386.57394

386.149

5588-33-0

Mesoridazine benzenesulfonate;32672-69-8

4078

Oily product

1.3g/cm3

570.5ºC at 760mmHg

Crystals from ethyl acetate; MP: 115-120 °C /tartrate/

298.9ºC

1.694

5.769

0

5

4

26

502

0

CN1CCCCC1CCN2C3=CC=CC=C3SC4=C2C=C(C=C4)S(=O)C

SLVMESMUVMCQIY-UHFFFAOYSA-N

InChI=1S/C21H26N2OS2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(26(2)24)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3

10-(2-(1-methylpiperidin-2-yl)ethyl)-2-(methylsulfinyl)-10H-phenothiazine

NC-123 NSC 186066 NSC-186066 NSC186066 TPS23 TPS 23 TPS-23 Thioridazine thiomethyl sulfoxide

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.)