Mechlorethamine

Structural formula
General
Non-proprietary name	Mechlorethamine
other names	N , N -bis (2-chloroethyl) - N -methylamine; Chloromethine; Nitrogen mustard; N-Lost; HN2;
Molecular formula	C 5 H 11 Cl 2 N
External identifiers / databases
ECHA InfoCard	100,000,110
PubChem	4033
DrugBank	DB00888
Wikidata	Q418011
Drug information
ATC code	L01 AA05
Drug class	Alkylating agents
properties
Molar mass	156.05 g mol −1
density	1.12 g cm −3 (at 25 ° C)
Melting point	−60 ° C ; 109–111 ° C (hydrochloride)
boiling point	87 ° C (at 24 hPa )
Vapor pressure	0.39 hPa (at 20 ° C)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 300-314-317-334-350
	P: 201-261-264-280-301 + 310-305 + 351 + 338
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Mechlorethamine (nitrogen mustard) is a drug selected from the group of alkylating agents , which as a cytostatic agent for the treatment of Hodgkin's disease is used ( trade name Mustargen ^® , USA, CH). The active ingredient is used as the hydrochloride .

Clinical information

Application areas (indications)

Mechlorethamine is used for palliative therapy in generalized Hodgkin's disease . It can also be used in bronchial carcinoma , generalized lymphosarcoma and locally in mycosis fungoides . In mycosis fungoides, application as an ointment can reduce the occurrence of allergic reactions . In studies of squamous cell carcinoma of the lung, it has shown advantages in patient survival over other alkylating agents .

It is not the therapy of choice for chronic leukemia or acute leukemia. It should remain limited to emergency situations if it is necessary to achieve a rapid reduction in a threateningly high white blood cell count.

Contraindications

In patients with thrombocytopenia , leukopenia and anemia caused by bone marrow involvement, the use should be weighed taking into account the risk of aggravation of these blood formation disorders. The use of mechlorethamine is contraindicated in the presence of infectious diseases.

Drug interactions

Vaccination with live virus vaccines should only be done after clarification of the haematological status, as mechlorethamine has an immunosuppressive effect.

Use during pregnancy and breastfeeding

Nitrogen mustard derivatives can cause fetal malformations, especially in early pregnancy. Therefore, when given to women, the likely risk should be weighed. Use in pregnant patients should be avoided until the third trimester .

unwanted effects

Nausea, vomiting and effects on the blood-forming system can force a dose limitation. Hair loss and hearing loss can occur. Loss of appetite, weakness and diarrhea have also been described during therapy with mechlorethamine.

Studies report an immunosuppressive effect of mechlorethamine. Mechlorethamine has been shown to have an inhibitory effect on the metabolism of lymphocytes. The use of mechlorethamine can predispose patients to bacterial, viral or fungal infections.
In vitro , mechlorethamine showed toxic effects on cells of the respiratory tract in mammals. Some of the patients who were treated for Hodgkin's disease according to the MOPP scheme (mechlorethamine, vincristine , procarbazine , prednisone ) developed secondary amenorrhea .

Pharmacological properties

Pharmacodynamics

As a biological alkylating agent, the cytotoxic effect of mechlorethamine is based on single and double strand breaks in the DNA of rapidly proliferating cells. The toxicity is high with an LD ₅₀ (rat, iv ) of 1.1 mg of the hydrochloride per kg of body weight.

Pharmacokinetics

After intravenous administration, it is rapidly converted into a reactive metabolite. Excretion takes place renally.

Other Information

History

Already during the Second World War, Alfred Gilman Sr. and Louis Goodman was in the laboratory of Thomas Dougherty demonstrating the induction of remissions on the transplanted lymphosarcoma mouse by N-Loste provide. In a study from 1942, a 47-year-old cancer patient ("JD") was treated for the first time with an nitrogen mustard (HN-3) (referred to there as "substance X"). Further studies were then carried out with HN-2. The results of these studies were not published until after the end of World War II.

literature

Apisarnthanarax et al .: Treatment of cutaneous T cell lymphoma: current status and future directions. In: American Journal of Clinical Dermatology . 2002, PMID 11978140

Web links

The Beginnings of Medical Oncology at the Mayo Clinic in Rochester (English)
Mechlorethamine on the opendrugdatabase
MedLinePlus Patient Drug Information

Individual evidence

↑ ^a ^b ^c ^d Entry on N-methylbis (2-chloroethyl) amine in the GESTIS substance database of the IFA , accessed on June 1, 2008(JavaScript required) .
↑ ^a ^b ^c Entry on chloromethine. In: Römpp Online . Georg Thieme Verlag, accessed on July 14, 2019.
↑ ^a ^b Data sheet Mechlorethamine hydrochloride from Sigma-Aldrich , accessed on April 9, 2011 ( PDF ).
↑ Hultgren et al. Topical nitrogen mustard for the treatment of granulomatous slack skin. In: American Journal of Clinical Dermatology . 2007, PMID 17298108 .
↑ Kim YH. Management with topical nitrogen mustard in mycosis fungoides. In: Dermatologic Therapy . 2003 PMID 14686971 .
↑ Kenar et al. Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism. Clin Chem Lab Med. 2006 PMID 17032138
↑ Purzyc et al. The influence of mechlorethamine on the activity of ecto-ATPase of rat lymphocytes. Ann Pharm Fr. 2001 PMID 11223577
↑ Giuliani et al. Toxic effects of mechlorethamine on mammalian respiratory mucociliary epithelium in primary culture. Cell Biol Toxicol . 1994 PMID 7895152
↑ Schilsky et al. L ong-term follow up of ovarian function in women Treated with MOPP chemotherapy for Hodgkin's disease. Am J Med, 1981 PMID 7282743
^ Alfred Gilman, Frederick S. Philips: The Biological Actions and Therapeutic Applications of the B-Chloroethyl Amines and Sulfides . In: Science . tape 103 , no. 2675 , April 5, 1946, pp. 409-436 , doi : 10.1126 / science.103.2675.409 , PMID 17751251 .
^ Alfred Gilman: The initial clinical trial of nitrogen mustard . In: The American Journal of Surgery (= Symposium on Current Status of Chemotherapy of Solid Tumors ). tape 105 , no. 5 , May 1, 1963, pp. 574-578 , doi : 10.1016 / 0002-9610 (63) 90232-0 .
^ John E. Fenn, Robert Udelsman: First Use of Intravenous Chemotherapy Cancer Treatment: Rectifying the Record . In: Journal of the American College of Surgeons . tape 212 , no. 3 , March 1, 2011, p. 413-417 , doi : 10.1016 / j.jamcollsurg.2010.10.018 .
^ Leon O. Jacobson et al .: NITROGEN MUSTARD THERAPY: Studies on the Effect of Methyl-Bis (Beta-Chloroethyl) Amine Hydrochloride on Neoplastic Diseases and Allied Disorders of the Hemopoietic System . In: Journal of the American Medical Association . tape 132 , no. 5 , October 5, 1946, p. 263-271 , doi : 10.1001 / jama.1946.02870400011003 .

[GESTIS-1] Entry on N-methylbis (2-chloroethyl) amine in the GESTIS substance database of the IFA , accessed on June 1, 2008(JavaScript required) .

[römpp-2] Entry on chloromethine. In: Römpp Online . Georg Thieme Verlag, accessed on July 14, 2019.

[Sigma-3] Data sheet Mechlorethamine hydrochloride from Sigma-Aldrich , accessed on April 9, 2011 ( PDF ).

[4] Hultgren et al. Topical nitrogen mustard for the treatment of granulomatous slack skin. In: American Journal of Clinical Dermatology . 2007, PMID 17298108 .

[5] Kim YH. Management with topical nitrogen mustard in mycosis fungoides. In: Dermatologic Therapy . 2003 PMID 14686971 .

[6] Kenar et al. Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism. Clin Chem Lab Med. 2006 PMID 17032138

[7] Purzyc et al. The influence of mechlorethamine on the activity of ecto-ATPase of rat lymphocytes. Ann Pharm Fr. 2001 PMID 11223577

[8] Giuliani et al. Toxic effects of mechlorethamine on mammalian respiratory mucociliary epithelium in primary culture. Cell Biol Toxicol . 1994 PMID 7895152

[9] Schilsky et al. L ong-term follow up of ovarian function in women Treated with MOPP chemotherapy for Hodgkin's disease. Am J Med, 1981 PMID 7282743

[10] Alfred Gilman, Frederick S. Philips: The Biological Actions and Therapeutic Applications of the B-Chloroethyl Amines and Sulfides . In: Science . tape 103 , no. 2675 , April 5, 1946, pp. 409-436 , doi : 10.1126 / science.103.2675.409 , PMID 17751251 .

[11] Alfred Gilman: The initial clinical trial of nitrogen mustard . In: The American Journal of Surgery (= Symposium on Current Status of Chemotherapy of Solid Tumors ). tape 105 , no. 5 , May 1, 1963, pp. 574-578 , doi : 10.1016 / 0002-9610 (63) 90232-0 .

[12] John E. Fenn, Robert Udelsman: First Use of Intravenous Chemotherapy Cancer Treatment: Rectifying the Record . In: Journal of the American College of Surgeons . tape 212 , no. 3 , March 1, 2011, p. 413-417 , doi : 10.1016 / j.jamcollsurg.2010.10.018 .

[13] Leon O. Jacobson et al .: NITROGEN MUSTARD THERAPY: Studies on the Effect of Methyl-Bis (Beta-Chloroethyl) Amine Hydrochloride on Neoplastic Diseases and Allied Disorders of the Hemopoietic System . In: Journal of the American Medical Association . tape 132 , no. 5 , October 5, 1946, p. 263-271 , doi : 10.1001 / jama.1946.02870400011003 .