D2 receptor

体外活性：吩噻嗪大部分在 10 位被二烷基氨基烷基取代，另外在 2 位被小基团取代，表现出有价值的活性，如精神安定、止吐、抗组胺、止痒、镇痛和抗蠕虫。 2-三氟甲基-10-(4-氨基丁基)phenothiazine 抑制 S. cerevisiae 菌株和 T. mentagrophites，MIC 分别为 0.4 μg/mL 和 1.5 μg/mL。 10-氨基甲酰基烷基吩噻嗪对革兰氏阳性枯草芽孢杆菌具有显着的活性，MIC 范围为 7.8 μg/mL–30 μg/mL。四环吩噻嗪（用萘醌环修饰）对金黄色葡萄球菌具有显着的抗菌活性，MIC50 为 12.5 μg/mL。带有丁烯接头的吩噻嗪比带有丙烯接头的吩噻嗪更有效，丙烯接头是 2-氯-10-氯乙基脲基丁基衍生物，针对 4 种白血病细胞系和 7 种结肠癌细胞系，其 GI50 分别为 1.4 μM 和 1.6 μM。 10-氨基（羟基）丙基吩噻嗪 (5 μM) 诱导人转化 WI38VA 细胞出现明显的细胞周期停滞 G2/M 期，随后在培养 2 天后发生细胞死亡。吩噻嗪类药物在体内经过广泛的代谢后被排出体外，主要是环羟基化、环磺氧化、N-去甲基化、N-氧化、硫酸化和葡萄糖醛酸结合。吩噻嗪对 α2 肾上腺素受体的结合亲和力比对多巴胺 D2 受体和 α1 肾上腺素受体的结合亲和力低得多。

Absorption, Distribution and Excretion
BECAUSE OF ITS LOW SOLUBILITY, RATE OF ITS ABSORPTION FROM GI TRACT IS DEPENDENT ON PARTICLE SIZE. MICRONIZED FORM OF DRUG IS ABSORBED RAPIDLY.
...ABOUT 30-50% OF ORAL DOSE PASSES THROUGH ALIMENTARY TRACT UNCHANGED. SOME PHENOTHIAZINE IS CONVERTED WITHIN GUT TO SOL DERIV...WHICH ARE ABSORBED INTO PORTAL VENOUS SYSTEM. ...DERIV ARE SECRETED IN URINE & ARE RESPONSIBLE FOR ITS RED COLOR WHEN EXPOSED TO AIR. THEY ALSO APPEAR IN BILE & IN MILK OF LACTATING ANIMALS. URINARY & FECAL EXCRETION OF PHENOTHIAZINE OR ITS DERIV ACCOUNTS FOR 80% OF ORAL DOSE IN SHEEP; FATE OF REMAINING 20% IS UNKNOWN.
URINARY & FECAL EXCRETION OF PHENOTHIAZINE OR ITS DERIV ACCOUNTS FOR 80% OF ORAL DOSE IN SHEEP; FATE OF REMAINING 20% IS UNKNOWN.
ABSORBED BY SKIN.
... Phenothiazine was readily absorbed from the alimentary tract, with the free drug and reddish oxidation products appearing in the urine.

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Metabolism / Metabolites
SOME PHENOTHIAZINE IS CONVERTED WITHIN GUT TO SOL DERIV, MAINLY PHENOTHIAZINE SULFATE...
YIELDS 3-HYDROXYPHENOTHIAZINE IN DOGS. /FROM TABLE/
THE ANTHELMINTIC, PHENOTHIAZINE, WAS OXIDIZED TO SULFOXIDE BY ENZYMES OF THE PROGLOTTIDS OF THE CESTODE, MONIEZIA EXPANSA & CYTOSOL OF INTESTINAL EPITHELIAL CELLS OF THE NEMATODE ASCARIS SUUM. ENZYMES IN THESE TISSUES ALSO DECR SULFOXIDES TO THIOETHERS IN ABSENCE OF O.
RAT, MOUSE, & GERBIL EXCRETED THE MAJORITY OF PHENOTHIAZINE IN CONJUGATED FORM. THE RAT, MOUSE, & GERBIL PRODUCED LEUCOPHENOTHIAZONE SULFATE AS MAJOR METABOLITE, RELYING MORE ON C-OXIDATION PATHS THAN THE HAMSTER WHICH EXCRETED LARGE AMT OF PHENOTHIAZINE N-GLUCURONIDE.

Interactions
PREVIOUS DRENCHING WITH CARBON TETRACHLORIDE MAY ALSO SERVE TO INCR ITS TOXICITY.
ANTIOXIDANTS, EG PHENOTHIAZINE, INHIBITED THE MUTAGENICITY OF BENZO(A)PYRENE & SOME OF ITS DERIVATIVES TOWARDS SALMONELLA TYPHIMURIUM STRAIN TA98; THIS INHIBITION WAS CONCN DEPENDENT.

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Non-Human Toxicity Values
LD50 Rat oral 5000 mg/kg.

[1]. Eur J Med Chem . 2011 Aug;46(8):3179-89.

[2]. Eur J Pharmacol . 1986 Jun 24;125(3):373-81.

[3]. J Antimicrob Chemother . 2001 May;47(5):505-11.

Phenothiazine is a light green to steel-blue powder. Acquires a greenish-brown tint under exposure to sunlight. (NTP, 1992)
10H-phenothiazine is the 10H-tautomer of phenothiazine. It has a role as a plant metabolite, a radical scavenger and a ferroptosis inhibitor. It is a tautomer of a 4aH-phenothiazine, a 1H-phenothiazine and a 3H-phenothiazine.
Phenothiazine (PTZ) is an organic thiazine compound.
Phenothiazine has been reported in Mimosa pudica with data available.
Phenothiazine is a class of agents exhibiting antiemetic, antipsychotic, antihistaminic, and anticholinergic activities. Phenothiazines antagonize the dopamine D2-receptor in the chemoreceptor trigger zone (CTZ) of the brain, potentially preventing chemotherapy-induced emesis. In addition, these agents have peripherally or centrally antagonistic activity against alpha adrenergic, serotonergic, histaminic, and muscarinic receptors. (NCI)
See also: Promethazine (has subclass); Chlorpromazine (has subclass); Trifluoperazine (has subclass) ... View More ...

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Therapeutic Uses
Antibiotics, Macrolide; Antiprotozoal Agents
AT ONE TIME EMPLOYED IN HUMAN MEDICINE AS ANTHELMINTIC & URINARY ANTISEPTIC.
MEDICATION (VET): ...EMPLOYED IN...VET MEDICINE FOR PINWORM, THREADWORM & ROUNDWORM INFESTATIONS. IT HAS ALSO BEEN USED AS URINARY ANTISEPTIC...
MEDICATION (VET): IT IS STILL OF VALUE FOR TREATMENT OF HELMINTHIASIS IN SHEEP & OTHER DOMESTIC ANIMALS.
For more Therapeutic Uses (Complete) data for PHENOTHIAZINE (8 total), please visit the HSDB record page.

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Drug Warnings
VET: ...ANIMALS.../HAVE/ DIED AFTER RECEIVING...THERAPEUTIC DOSE, WHEREAS OTHERS HAVE SURVIVED MANY TIMES THIS AMT. ...VARIATION IN TOXICITY...ADEQUACY OR OTHERWISE OF DIET, & PARTICULARLY ITS PROTEIN CONTENT, IS IMPORTANT FACTOR. DEHYDRATION IS ANOTHER, MORTALITY IN LAMBS BEING HIGHEST UNDER DROUGHT CONDITIONS. SUSCEPTIBILITY TO TOXIC EFFECTS...CONSIDERED...GREATEST IN HORSE, LESS SO IN DOG & PIG, WHILE RUMINANTS & BIRDS APPEAR...RESISTANT. ...TOXIC EFFECTS... MORE FREQUENTLY IN CATTLE THAN IN SHEEP & GOATS. YOUNG & DEBILITATED ANIMALS...MORE SUSCEPTIBLE... DIGESTIVE DISTURBANCES...PROMOTE ABSORPTION...
Use of the drug in weak animals, particularly those that are anemic and emaciated, is strictly contraindicated. Animals known to be constipated should not be treated with phenothiazine, since retention of the drug in the digestive tract and resulting absorption of greater than normal quantities is likely to lead to drug poisoning. Use of phenothiazine in pregnancy is contraindicated only during the last month of gestation.

C12H9NS

199.27

199.045

C, 72.33; H, 4.55; N, 7.03; S, 16.09

92-84-2

Phenothiazine-d8; 1219803-41-4

7108

Off-white to light green solid powder

1.2±0.1 g/cm3

371.0±12.0 °C at 760 mmHg

184 °C

178.2±19.6 °C

0.0±0.8 mmHg at 25°C

1.675

4.15

37.33

1

2

0

14

187

0

S1C2C(=CC=CC=2)NC2C1=CC=CC=2

WJFKNYWRSNBZNX-UHFFFAOYSA-N

InChI=1S/C12H9NS/c1-3-7-11-9(5-1)13-10-6-2-4-8-12(10)14-11/h1-8,13H

10H-phenothiazine

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)

配方 1 中的溶解度: ≥ 2.5 mg/mL (12.55 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (12.55 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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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。