Mechlorethamine alkylating agent

The antidote of choice for mechlorethamine extravasations is sodium thiosulfate. This agent binds alkylating agents, resulting in neutralization to inactive compounds that are then excreted. Sodium thiosulfate also may be effective for high-concentration cisplatin or dacarbazine extravasations. 

Mechlorethamine Mustargen) is a cytotoxic alkylating agent. Topical application of freshly prepared aqueous solutions are used in patients with early stages of cutaneous T-cell lymphoma. A major disadvantage to the use of this drug is the rapid induction of allergic contact dermatitis in some patients. 

Long-term complications such as cardiomyopathy (e.g., doxorubicin), leukemia (i.e., mechlorethamine), and infertility (alkylating agents) can also occur. Amelioration of certain side effects can be achieved with the judicious use of antiemetics and blood transfusions (or erythropoietin). 

Figure 13.7. Some alkylating agents and their reactions with DNA. a The N-mustard (di-[chloroethyl]-amine) group is found in several agents such as mechlorethamine and cyclophosphamide. b Successive reaction of the N-mustard group with two guanine bases, potentially forming a cross-link between the two strands of a DNA molecule, c Tautomerisation of guanine, after alkylation of its N7 position. Adenosine (bottom left) is shown for comparison.

Procarbazine is an alkylating agent that is used in the treatment of Hodgkin s disease in regimens such as MOPP (chlormethine (mechlorethamine), vincristine (Oncovin), procarbazine, and prednisolone) and BEACOPP (bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine, procarbazine, and prednisone) (1). It is also used to treat glioblastoma multiforme. 

The nitrogen mustard compound mechlorethamine (Fig 6.10) was the first alkylating agent to be used (1942). The nitrogen atom is able to displace a chloride ion intra-molecularly to form the highly electrophilic aziridine ion. Alkylation of DNA can then take place. Since the process can be repeated, cross-linking between chains will occur. 

Classic alkylating agents (mechlorethamine, melphalan, busulfan, chlorambucil, cyclophosphamide, ifosfamide)... 

Mechlorethamine HCl (Mustargen) was formerly used primarily in the combination chemotherapy regimen MOPP (mechlorethamine, vincristine [Oncovin], procarbazine, and prednisone) in patients with Hodgkin s disease. It is given by intravenous bolus administration in doses of 6 mg/m on days 1 and 8 of the 28-day cycles of each course of treatment. It has been largely replaced by cyclophosphamide, melphalan, and other more stable alkylating agents. It also is used topically for treatment of cutaneous T-cell lymphoma as a solution that is rapidly mixed and applied to affected areas of skin. 

Alkylating agents Nitrogen mustards Mechlorethamine Cyclophosphamide, chlorambucil... 

Mechlorethamine, the drug in Problem 45 that is in clinical use, is highly reactive so can be administered only by physicians who are experienced in its use. Explain why cyclophosphamide, carmustine, and chloroambucil are less reactive alkylating agents. 

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