Nitrofurans antibacterial action

Dantrolene, which is chemically related to the nitrofuran antibacterials (Chapter 7), was introduced as a myorelaxant with a unique direct action on skeletal muscle that reduces contractility by effecting Ca2+ release from the sarcoplasmic reticulum of certain muscle fibers. The CNS is not involved. The drug can control spasticity caused by spinal cord injuries, multiple sclerosis, cerebral palsy, and even strokes, but it is not indicated for arthritis or local acute spasms. 

The antibacterial action of several new nitrofurans in vitro against a number of organisms has been reported by Skagius . These data indicate that 5-(5-nitro-2-furyl)-2-amino-l,3,4-thiadiazole (NF-475, ASA-140, Ph/ 778, LXXI) and its formyl derivative LXXII) have been recommended for further study in the treatment of intestinal infections of various aetiology. 

Apart from their antibacterial action the nitrofurans have been tested as antiprotozoic, antihelminthic, antihypertensive and antineoplastic agents . The trials for these indications, however, are still in their neophyte stages, and it remains the task of future researchers to determine the importance of these additional indications for the nitrofurans. 

The mechanism of antibacterial action of the furan derivatives is unknown. However, the reduced forms of nitrofurans are highly reactive and are thought to inhibit many bacterial enzyme systems, including the oxidative decarboxylation of pyruvate to acetylcoenzyme A. Nitrofurans (see list in Table 1.7) are bacteriostatic but, at high concentrations, can be bactericidal to sensitive organisms. Both chromosomal and plasmid-mediated mechanisms of resistance to nitrofurantoin occur, and these most commonly involve the inhibition of nitrofuran reductase. 

Nitrofurazone. 2-[5-Nitro-2-furanyl)methylene]hydrazinecarboximide, the first nitrofuran to be employed clinically, is prepared from 5-nitro-2-furancarboxaldehyde and semicarbazide (19). This product has seen clinical use topically as an antibacterial, for systemic appHcation for bacterial infections in poultry and swine, and also has been employed as a food additive. In rats, nitrofurazone is hydroxjiated at the 4 position of the fiiran moiety (27). The involvement of nitreninm ions has also been postulated in the mechanism of action of nitrofurazone (38). 

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