Mesoridazine 以浓度依赖性方式抑制人 ether-a-go-go 相关基因 (HERG) 电流 (IC50 = 550 nM, 0 mV)。阻断作用沿着发生 HERG 激活的电压范围急剧增加，从而在达到 HERG 电压时导致最大可饱和通道活动 [1]。据报道，美索达嗪（15 mM；24 小时）在裸鼠和猪皮肤中的总吸收率分别为 15.94 ± 4.04% 和 39.24 ± 5.11% [3]。

美索达嗪 (15 mM) 在局部使用一次或每天一次持续 7 天时，在预防皮肤不适方面表现出强大的作用和持久的镇痛作用 [3]。裸鼠局部施用美索达嗪 (15 mM) 六小时。该药物的皮内浓度为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
Well absorbed from the gastrointestinal tract.
TOTAL URINARY & FECAL EXCRETION BY MONKEYS (10 DAY PERIOD) OF THIORIDAZINE WAS 64-76% & 83-92% FOR MESORIDAZINE (FECAL EXCRETION 2-4 TIMES GREATER). GREATER EXCRETION OF LATTER MAY BE DUE TO LESSER OVERALL TISSUE ADSORPTION OR LESS EXTENSIVE ENTERO-HEPATIC CYCLING.
WELL ABSORBED FROM GI TRACT. ONSET & DURATION OF ACTION & METABOLIC FATE... NOT...PRECISELY DETERMINED /HUMAN, ORAL, IM/. IN ANIMAL STUDIES, APPROX 2/3 OF DOSE...EXCRETED IN FECES VIA BILE & 1/3 OF DOSE...EXCRETED IN URINE. /BESYLATE/
PHENOTHIAZINES CROSS PLACENTAL BARRIER & MAY APPEAR IN MILK OF NURSING MOTHERS...PHENOTHIAZINES &...METABOLITES...EXCRETED IN URINE, BILE, & FECES. CERTAIN METABOLITES &...FREE DRUGS...DETECTED IN URINE UP TO 6 MO AFTER THERAPY...DISCONTINUED /HUMAN, ORAL, IM/
PHENOTHIAZINES...ABSORBED WELL FROM GI TRACT & FROM PARENTERAL SITES. GENERALLY...CLEARED FROM PLASMA WITHIN APPROX 3 HR...DISTRIBUTED TO MOST BODY TISSUES...HIGH CONCN OF UNCHANGED DRUG...IN BRAIN...METABOLITES PREDOMINATE IN LUNG, LIVER, KIDNEYS...SPLEEN /HUMAN, ORAL, IM/

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Metabolism / Metabolites
THIORIDAZINE-2-SULFOXIDE PROBABLY YIELDS THIORIDAZINE-2,5-DISULFOXIDE IN RAT: ZEHNDER, K ET AL, BIOCHEM PHARMAC, 11, 535 (1962). /FROM TABLE/
Thioridazine 2-sulfoxide is a known human metabolite of Thioridazine.

Half Life: 24 to 48 hours

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Biological Half-Life
24 to 48 hours

Toxicity Summary
Based upon animal studies, mesoridazine, as with other phenothiazines, acts indirectly on reticular formation, whereby neuronal activity into reticular formation is reduced without affecting its intrinsic ability to activate the cerebral cortex. In addition, the phenothiazines exhibit at least part of their activities through depression of hypothalamic centers. Neurochemically, the phenothiazines are thought to exert their effects by a central adrenergic blocking action.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because there is no published experience with mesoridazine during breastfeeding, other antipsychotic agents are preferred.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Phenothiazines cause galactorrhea in 26 to 40% of female patients. Hyperprolactinemia appears to be the cause of the galactorrhea. The hyperprolactinemia is caused by the drug's dopamine-blocking action in the tuberoinfundibular pathway. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Protein Binding
4%

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Toxicity Data
Oral LD₅₀ is 560 ± 62.5 mg/kg and 644 ± 48 mg/kg in mouse and rat, respectively.

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Interactions
CHLORPROMAZINE & OTHER ANTIPSYCHOTIC DRUGS...MAY BLOCK ANTIHYPERTENSIVE EFFECTS OF GUANETHIDINE. /CHLORPROMAZINE/
INTERACTIONS BETWEEN CHLORPROMAZINE & AMPHETAMINE, ALTHOUGH NOT DOCUMENTED, MAY APPLY TO OTHER PHENOTHIAZINE DERIV. /PHENOTHIAZINES/
PRETREATMENT WITH 3 MG/KG OF MESORIDAZINE-HCL ORALLY WAS MORE EFFECTIVE THAN THIORIDAZINE-HCL (6 MG/KG) IN DECR D-AMPHETAMINE SULFATE INDUCED BEHAVIOR IN DOGS.
Additive QT interval prolongation may increase the risk of ventricular tachycardia when /probucol is used with phenothiazines/. /Phenothiazines/
For more Interactions (Complete) data for MESORIDAZINE (31 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 MICE INTRAVENOUS 33 MG/KG /BESYLATE/
LD50 MICE SUBCUTANEOUS 611 MG/KG /BESYLATE/
LD50 MICE ORAL 346 MG/KG /BESYLATE/

[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 substituted at position 2 (para to the S atom) by a methylsulfinyl group, and on the nitrogen by a 2-(1-methylpiperidin-2-yl)ethyl group. It has a role as a dopaminergic antagonist and a first generation antipsychotic. It is a member of phenothiazines, a sulfoxide and a tertiary amino compound.
A phenothiazine antipsychotic with effects similar to chlorpromazine.
Mesoridazine is a Phenothiazine.
Mesoridazine has been reported in Phomopsis phaseoli with data available.
Mesoridazine is only found in individuals that have used or taken this drug. It is a phenothiazine antipsychotic with effects similar to chlorpromazine. [PubChem]Based upon animal studies, mesoridazine, as with other phenothiazines, acts indirectly on reticular formation, whereby neuronal activity into reticular formation is reduced without affecting its intrinsic ability to activate the cerebral cortex. In addition, the phenothiazines exhibit at least part of their activities through depression of hypothalamic centers. Neurochemically, the phenothiazines are thought to exert their effects by a central adrenergic blocking action.
A phenothiazine antipsychotic with effects similar to CHLORPROMAZINE.

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Drug Indication
Used in the treatment of schizophrenia, organic brain disorders, alcoholism and psychoneuroses.

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Mechanism of Action
Based upon animal studies, mesoridazine, as with other phenothiazines, acts indirectly on reticular formation, whereby neuronal activity into reticular formation is reduced without affecting its intrinsic ability to activate the cerebral cortex. In addition, the phenothiazines exhibit at least part of their activities through depression of hypothalamic centers. Neurochemically, the phenothiazines are thought to exert their effects by a central adrenergic blocking action.
...MECHANISM OF ACTION OF ANTIPSYCHOTIC DRUGS WITH RESPECT TO THERAPEUTIC EFFICACY & SIDE EFFECTS MAY RELATE TO INHIBITION OF DOPAMINE ACTIVATION OF ADENYLATE CYCLASE. /PHENOTHIAZINES/

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Therapeutic Uses
Antipsychotic Agents, Phenothiazine; Dopamine Antagonists
THE ANTIPSYCHOTIC DRUGS HAVE A HIGH THERAPEUTIC INDEX & ARE REMARKABLY SAFE AGENTS. FURTHERMORE, MOST PHENOTHIAZINES HAVE RELATIVELY FLAT DOSE-RESPONSE CURVE AND CAN BE USED OVER WIDE RANGE OF DOSAGES. ...SIDE EFFECTS ARE OFTEN EXTENSIONS OF MANY PHARMACOLOGICAL ACTIONS OF DRUGS... /PHENOTHIAZINES/
...INDICATED FOR MGMNT OF SCHIZOPHRENIA, ORG BRAIN DISORDERS, SYMPTOMS OF ALC WITHDRAWAL, & PSYCHONEUROSES. CLINICAL STUDIES TO DATE INDICATE THAT MESORIDAZINE BESYLATE HAS LOW INCIDENCE OF ADVERSE REACTIONS COMPARED WITH OTHER PHENOTHIAZINES. /BESYLATE/
8 WK THERAPY WITH THIORIDAZINE & MESORIDAZINE BESYLATE. THIORIDAZINE TREATED PT WERE SUPERIOR TO LATTER TREATED PT. IMPLICATIONS FOR CHEMOTHERAPY OF SCHIZOPHRENICS CONSIDERED.
For more Therapeutic Uses (Complete) data for MESORIDAZINE (6 total), please visit the HSDB record page.

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Drug Warnings
NEUROLEPTIC AGENTS ... SHOULD BE USED WITH EXTREME CAUTION, IF @ ALL, IN UNTREATED EPILEPTIC PT & IN PT UNDERGOING WITHDRAWAL FROM CENTRAL DEPRESSANT DRUGS SUCH AS ALCOHOL, BARBITURATES, OR BENZODIAZEPINES. MOST ANTIPSYCHOTIC DRUGS ... CAN BE USED SAFELY IN EPILEPTICS IF MODERATE DOSES ARE ATTAINED GRADUALLY AND IF CONCOMITANT ANTICONVULSANT DRUG THERAPY IS MAINTAINED. /PHENOTHIAZINES/
PHENOTHIAZINES INHIBIT EJACULATION WITHOUT INTERFERING WITH ERECTION. /PHENOTHIAZINES/
WT GAIN & INCR IN APPETITE OCCUR WITH ALL PHENOTHIAZINES... PERIPHERAL EDEMA OCCURS IN 1-3% OF PT & MAY BE OF ENDOCRINE ORIGIN. /PHENOTHIAZINES/
The antipsychotic drugs are not addicting ... However, some degree of physical dependence may occur, with malaise and difficulty in sleeping developing several days after abrupt discontinuation. Tolerance usually develops to the sedative effects ... over a period of days or weeks. Tolerance ... is demonstrable in behavioral and biochemical experiments in animals ... /Antipsychotic drugs/
For more Drug Warnings (Complete) data for MESORIDAZINE (20 total), please visit the HSDB record page.

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Pharmacodynamics
Mesoridazine, the besylate salt of a metabolite of thioridazine, is a phenothiazine tranquilizer. Pharmacological studies in laboratory animals have established that mesoridazine has a spectrum of pharmacodynamic actions typical of a major tranquilizer. In common with other tranquilizers it inhibits spontaneous motor activity in mice, prolongs thiopental and hexobarbital sleeping time in mice and produces spindles and block of arousal reaction in the EEG of rabbits. It is effective in blocking spinal reflexes in the cut and antagonizes d-amphetamine excitation and toxicity in grouped mice. It shows a moderate adrenergic blocking activity in vitro and in vivo and antagonizes 5-hydroxytryptamine in vivo. Intravenously administered, it lowers the blood pressure of anesthetized dogs. It has a weak antiacetylcholine effect in vitro.

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

68.06

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。