Mechlorethamine HCl   中文名称: 盐酸氮芥

体外活性：与有氧条件下相比，氮芥在氮气条件下对大鼠肝细胞的毒性要小得多，并且引起的脂质过氧化要少得多。氮芥显着抑制细胞生长，并导致与兔气管原代培养物中细胞骨架蛋白重排相关的细胞脱离。二氯乙胺导致兔气管原代培养物中早期脂质过氧化和细胞膜损伤，这与抗氧化酶活性显着增加相关，而抗氧化酶活性显着增加，而抗氧化酶活性显着增加，而抗氧化酶活性显着增加，而谷胱甘肽含量增加

MeChlorethamine (1.5 mg/kg iv) 可将兔子的平均白细胞计数从 6,320 mm3 降低至 1,890 mm3，但对白细胞分类或红细胞和血小板计数没有任何变化。氮芥（0.005 mg-0.5 mg，id）会引起小鼠剂量依赖性皮肤溃疡，在氮芥后立即给予等渗硫代硫酸钠（0.167 M）或高渗（0.34 M）（0.05 mL）可显着减少平均 HN2 溃疡面积和溃疡的总时间。

Absorption, Distribution and Excretion
Following IV injection, the drug undergoes rapid chemical transformation and unchanged mechlorethamine is undetectable in the blood within a few minutes. Less than 0.01% of an IV dose is excreted unchanged in the urine.
Mice given 35 mg/kg body wt mechlorethamine hydrochloride iv and examined by autoradiography had significant levels of compound in brain, spinal cord, lung and submaxillary glands.
Mechlorethamine is incompletely absorbed following intracavitary administration, probably because of rapid deactivation by body fluids.

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Metabolism / Metabolites
Following its in vivo admin, mechlorethamine or its hydrochloride is probably converted into ethyleneimmonium ion which reacts with guanine residues in /either the same or/ adjacent strands of DNA as well as with SH groups.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Most sources consider that mothers receiving antineoplastic therapy should not breastfeed, especially with alkylating agents such as mechlorethamine. Because of the potential for serious adverse reactions in the breastfed infant, breastfeeding from mechlorethamine mothers should not breastfed during therapy with mechlorethamine therapy, including topical application.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Interactions
Morphine and pethidine hydrochloride significantly potentiated mechlorethamine hydrochloride toxicity. The potentiation seems dose related. Morphine converted sublethal doses of mechlorethamine to maximal LD's.
In HT29 human colon carcinoma cells, amphotericin b (approx 120 ug/ml) increased uptake of mechlorethamine hydrochloride due to increases in vmax without change in km.
Mechlorethamine may raise the concentration of blood uric acid; dosage adjustment of antigout agents may be necessary to control hyperuricemia and gout; allopurinol may be preferred to prevent or reverse mechlorethamine-induced hyperuricemia because of risk of uric acid nephropathy with uricosuric antigout agents.
Leukopenic and/or thrombocytopenic effects of mechlorethamine may be increased with concurrent or recent therapy /with blood dyscrasia-causing medications/ if these medications cause the same effects; dosage adjustment of mechlorethamine, if necessary, should be based on blood counts.
For more Interactions (Complete) data for MECHLORETHAMINE HYDROCHLORIDE (8 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat iv 1.1 mg/kg
LD50 Rat sc 1.9 mg/kg

[1]. Effect of brentuximab vedotin combined with chlormethine hydrochloride on the treatment of 6 patients with relapsed and refractory Hodgkin lymphoma. Zhonghua Xue Ye Xue Za Zhi. 2015 Jul 14;36(7):575-577.

Nitrogen Mustard Hydrochloride (Mechlorethamine Hydrochloride) can cause cancer according to an independent committee of scientific and health experts. It can cause developmental toxicity according to state or federal government labeling requirements.
Nitrogen mustard hydrochloride appears as white to off-white crystals or powder with a fishy odor. Initial pH (2% aqueous solution) 3.0-4.0. (NTP, 1992)
Mechlorethamine hydrochloride is the hydrochloride salt of mechlorethamine. It has a role as an antineoplastic agent. It contains a mechlorethamine.
Mechlorethamine Hydrochloride is the hydrochloride salt of mechlorethamine, a nitrogen mustard and an analogue of sulfur mustard, with antineoplastic and immunosuppressive activities. Mechlorethamine is metabolized to an unstable, highly reactive ethyleniminium intermediate that alkylates DNA, particularly the 7 nitrogen of guanine residues, resulting in DNA base pair mismatching, DNA interstrand crosslinking, the inhibition of DNA repair and synthesis, cell-cycle arrest, and apoptosis. This agent also exhibits lympholytic properties.
A biologic alkylating agent that exerts its cytotoxic effects by forming DNA ADDUCTS and DNA interstrand crosslinks, thereby inhibiting rapidly proliferating cells. The hydrochloride is an antineoplastic agent used to treat HODGKIN DISEASE and LYMPHOMA.

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Mechanism of Action
Mechlorethamine, as an alkylating agent, interferes with DNA replication and transcription of RNA and ultimately results in the disruption of nucleic acid function. Mechlorethamine also possesses weak immunosuppressive activity.
Mechlorethamine, as an alkylating agent, interferes with DNA replication and transcription of RNA, and ultimately results in the disruption of nucleic acid function.

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Therapeutic Uses
Alkylating Agents; Antineoplastic Agents, Alkylating;
Antineoplastic
VET: Antineoplastic
MEDICATION (VET): ... MECHLORETHAMINE HYDROCHLORIDE IS REPORTED TO BE USED FOR TREATMENT OF LYMPHOSARCOMA & OF MAST CELL SARCOMA IN DOGS & OF FOWL LEUKOSIS ... /MECHLORETHAMINE HYDROCHLORIDE/
For more Therapeutic Uses (Complete) data for MECHLORETHAMINE HYDROCHLORIDE (11 total), please visit the HSDB record page.

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Drug Warnings
Adverse CNS effects which have occurred following IV administration of mechlorethamine include weakness, headache, drowsiness, vertigo, lightheadedness, convulsions, progressive muscle paralysis, paresthesia, cerebral degeneration, coma, and death. Serious neurotoxicity appears to be a problem only when high doses or intra-arterial and regional perfusion administration techniques are used. Immediate and delayed neurotoxicity, sometimes severe, has been reported in patients receiving higher than recommended doses of the drug in preparation for bone marrow transplantation; neurotoxicity appeared to increase with age and dose administered and occurred more frequently in patients who also received procarbazine or cyclophosphamide.
Adverse dermatologic effects of systemic mechlorethamine therapy occasionally include a maculopapular skin eruption which is apparently idiosyncratic. The maculopapular skin eruption does not necessarily recur with subsequent doses and is not a contraindication to future use of the drug. Erythema multiforme also has been reported. Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving IV mechlorethamine. ... Herpes zoster, which occurs commonly in patients with lymphoma, may be precipitated by treatment with mechlorethamine.
Major and dose-limiting adverse effects of mechlorethamine are nausea and vomiting, which occur in up to 90% of patients who receive the drug and are presumably due to CNS stimulation.Vomiting, which may be severe enough to precipitate vascular accidents in patients with hemorrhagic tendencies, occurs within 0.5-8 hours (usually 1-3 hours) after administration of mechlorethamine. Emesis generally subsides within 8 hours, but nausea may persist 24 hours or longer. ... Other GI effects of mechlorethamine include anorexia, diarrhea, severe hematemesis and dehydration secondary to vomiting, and rarely, peptic ulcers.
Mechlorethamine must be used with extreme caution in patients with leukopenia, thrombocytopenia, or anemia caused by infiltration of bone marrow with malignant cells. In these patients, a good response to mechlorethamine therapy with disappearance of tumor from the bone marrow may be associated with improved bone marrow function; however, in the absence of good response or in patients who have received previous treatment with antineoplastic agents, hematopoiesis may be further compromised, resulting in more severe leukopenia, thrombocytopenia, anemia, and possibly death. Patients with chronic lymphocytic leukemia appear to be especially sensitive to the hematopoietic effects of mechlorethamine and should receive the drug with extreme caution, if at all.
For more Drug Warnings (Complete) data for MECHLORETHAMINE HYDROCHLORIDE (17 total), please visit the HSDB record page.

C5H11CL2N.HCL

192.51

191.003

C, 31.19; H, 6.28; Cl, 55.25; N, 7.28

55-86-7

51-75-2 55-86-7 (HCl)

5935

Hygroscopic leaflets from acetone or chloroform
White hygroscopic crystals
White, crystalline, hygroscopic powder

1.106g/cm3

110.3ºC at 760 mmHg

108-111 °C(lit.)

20.5ºC

1.4689 (24ºC)

2.197

3.24

1

1

4

9

43.7

0

ClC([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])Cl.Cl[H]

QZIQJVCYUQZDIR-UHFFFAOYSA-N

InChI=1S/C5H11Cl2N.ClH/c1-8(4-2-6)5-3-7;/h2-5H2,1H3;1H

2-chloro-N-(2-chloroethyl)-N-methylethanamine;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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: ≥ 2.08 mg/mL (10.80 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 20.8 mg/mL澄清DMSO储备液加入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: ≥ 2.08 mg/mL (10.80 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (10.80 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 20.8 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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配方 4 中的溶解度: 100 mg/mL (519.45 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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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。