Mesna

Several mucolytics reduce the viscosity of mucus by cleaving the disulfide bonds that maintain the gel stmcture. AJ-Acet l-L-cysteine [616-91 -1] (19), introduced in 1963, and mesna [19677-45-5] (20), developed in Europe in the early 1970s (20,21), are effective compounds in this class. Whereas most mucolytics must be adrninistered by aerosol, carbocysteine [638-23-6] (21), which contains a derivatized sulfhydryl group, has shown activity by the oral route (22,23). However, carbocysteine does not reduce mucus viscosity, as does acetylcysteine, but appears to have a direct action on mucus glycoprotein production (24). 

Sodium 2-mercaptoethanesulfonate (MESNA) [19767-45-4] M 164.2, pKj <0 (SOj ), pK 9.53 (SH). It can be recrystd from H2O and does not melt below 250°. It can be purified further by converting to the free acid by passing a 2M soln through an ion exchange (Amberlite IR-120) column in the acid form, evaporating the eluate in a vacuum to give the acid as a viscous oil (readily dec) which can be checked by acid and SH titration. It is then dissolved in H2O, carefully neutralised with aqueous NaOH, evaporated and recrystd from H2O [7 Am Chem Soc 77 6231 1955]. 

A pivalamide of an indole, introduced with PvCl (NaH, DMF, 0°, 1 h, 96% yield), is efficiently cleaved with MeSNa (MeOH, 20°, 2 h, 96% yield). 

Table 7.1. Denitration of nitro eomponnds with MeSNa or 8038111 ...

Bii3SnH, (PhCOlaOa benzene, 18 h MeSNa HMPA, 16 h Bii3SnH, (PhCOlaOa benzene, 18 h MeSNa DMF, 8h... 

Clinical trials showed therapeutic efficacy in a broad spectrum of tumors these include SCLC, testicular tumors, sarcomas, breast cancer, renal cell cancer, pancreatic tumors and lymphomas. Ifosfamide is less myelosuppressive than cyclophosphamide but is more toxic to the bladder. Therefore it is recommended that ifosfamide is coadministered with the thiol compound mesna to avoid hemorrhagic cystitis and to reduce the risk of developing bladder cancer. Other side effects include neurotoxicity and myelosuppression. 

Few side effects can be alleviated by the use of antidotes. An example is the prevention of hemorrhagic cystitis caused by cyclophosphamide by the concomitant infusion of mesna. 

Ajmal, N. et al. The effectiveness of sodium 2-mercaptoethane sulfonate (Mesna) in reducing capsular formation around implants in a rabbit model. Blast. Reconstr. Surg., 112, 1455, 2003. 

Cyclophosphamide Hemorrhagic cystitis due to acrolein metabolite (prevent with MESNA)... 

ACE-I, angiotensin-converting enzyme inhibitor ADH, antidiuretic hormone (or vasopressin) ARB, angiotensin II receptor blocker, MESNA, sodium 2-mercaptoethanesulfonate TCA, tricyclic antidepressant Ul, urinary incontinence SUI, stress urinary incontinence UUI, urge urinary incontinence. 

The use of effective prevention strategies can decrease the incidence of hemorrhagic cystitis to less than 5% in patients receiving cyclophosphamide or ifosfamide. There are three methods to reduce the risk administration of mesna, hyperhydration, and bladder irrigation with catheterization. 

Continuous bladder irrigation by catheterization uses normal saline at 250 to 1000 mL/hour to flush acrolein from the bladder. Hyperhydration with normal saline at 3 L/m2 per day with intravenous furosemide to maintain urine output greater than 100 mL/hour also has been used with cyclophosphamide. Mesna is equivalent to both strategies in patients receiving high-dose cyclophosphamide and avoids the discomfort and... 

TABLE 96-9. ASCO Guidelines for the Use of Mesna with Ifosfamide and High-Dose Cyclophosphamide... 

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