関: mechlorethamine、nitrogen mustard

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/31 03:48:58」(JST)

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Chlormethine (INN, BAN), mechlorethamine (widely used in the US, not the USAN, however) also known as mustine and HN2 and in former USSR known as Embichin is a nitrogen mustard sold under the brand name Mustargen. It is the prototype of alkylating agents, a group of anticancer chemotherapeutic drugs. It works by binding to DNA, crosslinking two strands and preventing cell duplication. It binds to the N7 nitrogen on the DNA base guanine. As the chemical is a blister agent, its use is strongly restricted within the Chemical Weapons Convention where it is classified as a Schedule 1 substance.

Mechlorethamine belongs to the group of nitrogen mustard alkylating agents.^[1]^[2]

Uses

It has been derivatized into the estrogen analogue estramustine, used to treat prostate cancer. It can also be used in chemical warfare where it has the code-name HN2. This chemical is a form of nitrogen mustard gas and a powerful vesicant. Historically, some uses of mechlorethamine have included lymphoid malignancies such as Hodgkin’s disease, lymphosarcoma, chronic myelocytic leukemia, polycythemia vera, and bronchogenic carcinoma ^[3] Mechlorethamine is often administered intravenously,^[4] but when compounded into a topical formulation it can also be used to treat skin diseases. There have been studies demonstrating that topical administration of mechlorethamine has efficacy in mycosis fungoides-type cutaneous T cell lymphoma ^[5]^[6]^[7]

Another important use of chlormethine is in the synthesis of meperidine (aka pethidine, demerol).

Side effects

Mechlorethamine is a highly toxic medication, especially for women who are pregnant, breastfeeding, or of childbearing age.^[8]^[9]

The adverse effects of mechlorethamine depend on the formulation.^[10] Adverse effect include:

“Hypersensitivity reactions, including anaphylaxis…. Nausea, vomiting and depression of formed elements in the circulating blood are dose-limiting side effects and usually occur with the use of full doses of MUSTARGEN. Jaundice, alopecia, vertigo, tinnitus and diminished hearing may occur infrequently. Rarely, hemolytic anemia associated with such diseases as the lymphomas and chronic lymphocytic leukemia may be precipitated by treatment with alkylating agents including MUSTARGEN. Also, various chromosomal abnormalities have been reported in association with nitrogen mustard therapy.”

History

Successful clinical use of chlormethine (mechlorethamine) resulted in development of the field of anticancer chemotherapy, led by Cornelius P. Rhoads at Memorial Sloan-Kettering. The drug is a nitrogen-based analogue of mustard gas (which is sulfur-based) and was derived from chemical warfare research. Secret clinical trials of the agent for Hodgkin's disease and several other lymphomas and leukemias in humans began in December 1942. Because of wartime secrecy restrictions, it was not until 1946 that the results of these trials were published openly.^[11]

References

^ Rappeneau S, Baeza-Squiban A, Jeulin C, Marano F (March 2000). "Protection from cytotoxic effects induced by the nitrogen mustard mechlorethamine on human bronchial epithelial cells in vitro". Toxicol. Sci. 54 (1): 212–21. doi:10.1093/toxsci/54.1.212. PMID 10746948.
^ Takimoto CH, Calvo E. "Principles of Oncologic Pharmacotherapy" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.
^ Bunn P, Hoffman S, Norris D, Golitz L, Aeling J. Systemic therapy of cutaneous T-cell lymphoma (mycosis fungoides and the Sezary syndrome). Ann Intern Med. 1994; 121(8):592–602. [PubMed:8085692]
^ Medline (2012). Mechlorethamine. Retrieved from http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682223.html
^ Lindahl LM, Fenger-Gron M, Iversen L. Topical nitrogen mustard therapy in patients with mycosis fungoides or parapsoriasis. J Eur Acad Dermatol Venereol. 2013 Feb;27(2):163-8.
^ Galper SL, Smith BD, Wilson LD. Diagnosis and management of mycosis fungoides. Oncology (Williston Park). 2010 May;24(6):491-501.
^ Lessin SR, Duvic M, Guitart J, Pandya AG, Strober BE, Olsen EA, Hull CM, Knobler EH, Rook AH, Kim EJ, Naylor MF, Adelson DM, Kimball AB, Wood GS, Sundram U, Wu H, Kim YH. Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol. 2013 Jan;149(1):25-32.
^ Recordati Rare Diseases Inc. (2013). Mustargen Package Insert. Retrieved from http://www.drugs.com/pro/mustargen.html
^ Actelion Pharmaceuticals Ltd. (2013) Valchlor Package Insert. Retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf
^ Mustargen and Valchlor
^ Gilman A. (1963). "The initial clinical trial of nitrogen mustard". Am J Surg. 105 (5): 574–578. doi:10.1016/0002-9610(63)90232-0. PMID 13947966.

External links

British Columbia Cancer Agency profile

English Journal

Preparation of Conjugated Polymer Grafted with H2O2-Sensitive Prodrug for Cell Imaging and Tumor Cell Killing.

Li M, Li S, Chen H, Hu R, Liu L, Lv F, Wang S.
ACS applied materials & interfaces.ACS Appl Mater Interfaces.2015 Dec 29. [Epub ahead of print]
In this work, a new conjugated polymer poly (fluorene-co-phenylene) derivative containing pendent quaternized chlormethine (PFP-Chl) was synthesized by covalent linking small molecular prodrug groups onto conjugated polymer side chains. H2O2-sensitive prodrug with an eight-member-cyclic boronate est
PMID 26713684

Spermatogenesis in Hodgkin's lymphoma patients: a retrospective study of semen quality before and after different chemotherapy regimens.

Paoli D1, Rizzo F1, Fiore G1, Pallotti F1, Pulsoni A2, Annechini G2, Lombardo F1, Lenzi A1, Gandini L3.
Human reproduction (Oxford, England).Hum Reprod.2015 Dec 23. pii: dev310. [Epub ahead of print]
STUDY QUESTION: Is spermatogenesis impairment caused by Hodgkin's lymphoma (HL) itself or by the various treatments SUMMARY ANSWER: HL is not itself the main cause of impaired spermatogenesis, which is instead affected by the treatment; the extent of impairment depends on the type of treatment and t
PMID 26705149

Optimizing Care and Compliance for the Treatment of Mycosis Fungoides Cutaneous T-Cell Lymphoma With Mechlorethamine Gel.

Benjamin Chase A1, Markel K2, Tawa MC.
Clinical journal of oncology nursing.Clin J Oncol Nurs.2015 Dec 1;19(6):E131-9. doi: 10.1188/15.CJON.E131-E139.
BACKGROUND: Mycosis fungoides is the most common form of cutaneous T-cell lymphoma (MF-CTCL). Quality nursing care is necessary for effective diagnosis and treatment of patients with MF-CTCL. Early-stage MF-CTCL (stages Ia and Ib) is most often managed in both dermatology and multidisciplinary setti
PMID 26583648

「メクロレタミン」

Chlormethine
Names
	IUPAC name Bis(2-chloroethyl)methylamine
Identifiers
CAS Registry Number	51-75-2
ATC code	D08AX04; L01AA05
ChEBI	CHEBI:28925
ChEMBL	ChEMBL427
ChemSpider	3893
DrugBank	DB00888
EC number	200-120-5
	InChI InChI=1S/C5H11Cl2N/c1-8(4-2-6)5-3-7/h2-5H2,1H3 ; Key: HAWPXGHAZFHHAD-UHFFFAOYSA-N ;
Jmol-3D images	Image
KEGG	D0767
MeSH	Mechlorethamine
PubChem	4033
	SMILES CN(CCCl)CCCl ;
UNII	50D9XSG0VR
Properties
Chemical formula	C5H11Cl2N
Molar mass	156.05 g·mol−1
Appearance	Colourless liquid
Odor	Ichtyal, ammoniacal
log P	0.91
Pharmacology
Legal status	℞ (Prescription only);
Pregnancy; category	US: D (Evidence of risk);
Routes of; administration	Intracavitary; Intrapericardial; Intravenous; Topical;
	Pharmacokinetics:
Biological half-life	<1 minute
Excretion	50% (renal)
Related compounds
Related amines	Dimethylamine; Trimethylamine; N-Nitrosodimethylamine; Diethylamine; Triethylamine; Diisopropylamine; Dimethylaminopropylamine; Diethylenetriamine; N,N-Diisopropylethylamine; Triisopropylamine; Tris(2-aminoethyl)amine; HN1 (nitrogen mustard); HN3 (nitrogen mustard);
Related compounds	Unsymmetrical dimethylhydrazine; Biguanide; Dithiobiuret; Agmatine;
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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	Infobox references

　　[★]

英: mechlorethamine
関: ナイトロジェンマスタード nitrogen mustard、クロルメチン chlormethine、mustargen

ナイトロジェンマスタードの別名

「クロルメチン」

　　[★]

英: chlormethine
関: ナイトロジェンマスタード、メクロレタミン

[pmid10746948-1] Rappeneau S, Baeza-Squiban A, Jeulin C, Marano F (March 2000). "Protection from cytotoxic effects induced by the nitrogen mustard mechlorethamine on human bronchial epithelial cells in vitro". Toxicol. Sci. 54 (1): 212–21. doi:10.1093/toxsci/54.1.212. PMID 10746948.

[2] Takimoto CH, Calvo E. "Principles of Oncologic Pharmacotherapy" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.

[3] Bunn P, Hoffman S, Norris D, Golitz L, Aeling J. Systemic therapy of cutaneous T-cell lymphoma (mycosis fungoides and the Sezary syndrome). Ann Intern Med. 1994; 121(8):592–602. [PubMed:8085692]

[4] Medline (2012). Mechlorethamine. Retrieved from http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682223.html

[5] Lindahl LM, Fenger-Gron M, Iversen L. Topical nitrogen mustard therapy in patients with mycosis fungoides or parapsoriasis. J Eur Acad Dermatol Venereol. 2013 Feb;27(2):163-8.

[6] Galper SL, Smith BD, Wilson LD. Diagnosis and management of mycosis fungoides. Oncology (Williston Park). 2010 May;24(6):491-501.

[7] Lessin SR, Duvic M, Guitart J, Pandya AG, Strober BE, Olsen EA, Hull CM, Knobler EH, Rook AH, Kim EJ, Naylor MF, Adelson DM, Kimball AB, Wood GS, Sundram U, Wu H, Kim YH. Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol. 2013 Jan;149(1):25-32.

[8] Recordati Rare Diseases Inc. (2013). Mustargen Package Insert. Retrieved from http://www.drugs.com/pro/mustargen.html

[9] Actelion Pharmaceuticals Ltd. (2013) Valchlor Package Insert. Retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf

[10] Mustargen and Valchlor

[11] Gilman A. (1963). "The initial clinical trial of nitrogen mustard". Am J Surg. 105 (5): 574–578. doi:10.1016/0002-9610(63)90232-0. PMID 13947966.

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案内

chlormethine