Mechlorethamine nitrogen mustard

Mechlorethamine (nitrogen mustard) In vivo each chloroethylamine group undergoes intramolecular cy-clization with release of a chloride ion. The so formed highly reactive ethylen-immonium derivative alkylates DNA and other biomolecules and causes the cytotoxic effect. 

Mechlorethamine (nitrogen mustard Mustargen), a derivative of the war gas sulfur mustard, is considered to be the first modern anticancer drug. In the early 1940s it was discovered to be effective in the treatment of human lymphomas. 

M3. Marshall, W. H., Hoppe, E. T., and Stark, F., The effect of ambient oxygen tension on the toxicity and therapeutic effect of mechlorethamine (nitrogen mustard). Arch. Surg. 86, 932-939 (1963). 

Cyclophosphamide may be of benefit to some patients with other serious, refractory manifestations of lupus, iucludiug ueuro-logic manifestations. Reports of the use of other cytotoxic drugs for lupus in recent years include methotrexate, mycophenolate mofetil, " mechlorethamine (nitrogen mustard), chlorambucil, and cyclosporine. " ... 

Mechlorethamine (nitrogen mustard H2N Mustargen) HD NHL Mycosis fungoides (topical)... 

Agent HN2 [bis(2-chloroethyl)methylamine mechlorethamine nitrogen mustard CAS no. 51-75-2] is a clear to yellow liquid (see Table 4). Its chemical structure is... 

Nitrogen mustard is clinically used for the treatment of lymphomas and some forms of lung cancer. The major indication for mechlorethamine is Hodgkin s disease as a part of the MOPP regimen (mechlorethamine + vincristine (oncovin) + procarbazine + prednisone). The usual dose consists of 6 mg/m2 on days 1 and 8. This drug has pronounced hematological toxicity (myelo-suppression). 

Fig. 11.5. Mechanism of hydrolytic dechlorination of mechlorethamine (11.31, R = Me) and other antitumor nitrogen mustards [65] [66]. Also shown is the mechanism of the nonenzymat-ic conjugation with reduced glutathione (GSH, L-glutamyl-L-cysteinylglycine).

Epstein JH Nitrogen mustard (mechlorethamine) and UVB photocarcinogenesis a dose response effect. J Invest Dermatol 83 320-322, 1984... 

The nitrogen mustard analogues are nitrogen derivatives of sulfur mustard, used as poison gas in World War I. Agents include cyclophosphamide, mechlorethamine, chlorambucil, melphalan, ifos-famide, uramustine and estramustine. 

Mechlorethamine was the first nitrogen mustard. It is directly toxic. With its half-life of only a few minutes infusion directly into arteries supplying the tumor is the preferred mode of administration. Its spectrum of adverse effects is similar to that of cyclophosphamide. 

The major indication for mechlorethamine is Hodgkin s disease the drug is given in the MOPP regimen (mechlorethamine, vincristine, procarbazine, prednisone see Chapter 55). Other less reactive nitrogen mustards are now preferred for the treatment of non-Hodgkin s lymphomas, leukemias, and various solid tumors. 

Melphalan (Alkeran) is an amino acid derivative of mechlorethamine that possesses the same general spectrum of antitumor activity as do the other nitrogen mustards. However, the bioavailability of the oral preparation is quite variable (25-90%) from one patient to another. 

Chlorambucil (Leukeran) is an aromatic nitrogen mustard that is intermediate in chemical reactivity between mechlorethamine and melphalan. Its mechanisms of action and range of antitumor activity are similar to theirs. It is well absorbed orally, but detailed information concerning its metabolic fate in humans is lacking. 

Mechlorethamine Mustargen, nitrogen mustard Bronchogenic carcinoma chronic leukemia Hodgkin disease non-Hodgkin lymphomas blood disorders (leukopenia, thrombocytopenia] skin rashes/itching Blood disorders (anemia, leukopenia, thrombocytopenia] Gl distress (nausea, vomiting] CNS effects (headache, dizziness, convulsions] local irritation at injection site... 

A large number of medications are amines, and a few examples are shown in Figure 11.29. It is interesting to note that mechlorethamine, one of the first anticancer chemotherapy drugs, belongs to a class of compounds known as nitrogen mustards, the same class of compounds used in chemical warfare during World War I. 

Mechlorethamine [me klor ETH a meen] was developed as a vesicant (nitrogen mustard) during World War I. Its ability to cause lymphocytopenia led to its use in lymphatic cancers. Because it can bind and react at two separate sites, it is called a bifunctional agent. ... 

EMBICHIN ENT 25,294 HN2 MBA MECHLORETHAMINE N-METHYL-BIS-CHLORAETHYLAMIN (GERMAN) METHYLBIS(P-CHLOROETHYL)AMINE N-METHYL-BIS(p-CHLOROETHYL)AMINE N-METHYL-BIS(2-CHLOROETHYL)AMINE (MAK) N-METHYL-2,2 -DICHLORODIETHYLAMINE METHYLDI(2-CHLOROETHYL)AMINE N-METHYL-LOST MUSTARGEN MUSTINE MUTAGEN NITROGEN MUSTARD N-LOST (GERMAN) NSC-762 TL 146... 

SYNS 2,2 -DICHLORO-N-METH [ LDIETHYLAi IINE-N-OXIDE DIETHYLAMINE, 2,2 -DICHLORO-N-METH-YL-, OXIDE HN2 AxMINE OXIDE HN2 OXIDE MUSTARD xMBAO MECHLORETHAMINE OXIDE METHYL-BIS(P-CHLOROETHYL)Ai nNE OXIDE METHYLBIS(P-CHLOROETHYL)AMINE N-OXIDE N-METH [ L-DI-2-CHLOROETHYL. MI E-N-OXIDE MITOMEN MITOMIN NITROGEN MUSTARD OXIDE NITROGEN MUSTARD-N-OXIDE NTTROMIN NMO N-OXYD-LOST N-OXYD-xMUSTARD NSC-10107 OXY-NH2... 

Chlormethine (mechlorethamine, mustine, nitrogen mustard) is mainly used topically in the early stages of mycosis fungoides (4). 

Mechlorethamine hydrochloride Nitrogen mustard topical antimitotic drug Carcinogen suppression of immunological defences Stevens-Johnson syndrome (SEDA-22, 172) (19)... 

Aryl-subslituled nitrogen mustards such as chlorambucil are relatively stable to aziridinium ion fonnation because (he aromatic ring decreases the nucleophilicity of the nitni-gen atom. These mustards react according to first-order ki-netics. " The stability of chlorambucil allows it to be taken orally, whereas mechlorethamine is given by intravenous administration of freshly prepared solutions. The Kquiic-ment for fre.shly prepared solutions is bused on (he gnidml decomposition of the aziridinium ion by interaction willi water. 

Nitrogen mustard will hereafter be referred to by its generic name, mechlorethamine, and generic names will be used for all drugs. Trade names for some are listed in Appendix 1. 

HN-3 Tris(2-chloroethyl)amine 2-Chloro-N,N-bis(2-chloroethyl)ethanamine Trichlorotriethyla-mine Nitrogen mustard-3 Mechlorethamine Mustargen... 

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