Synergistic Activities of Nitric Oxide and Various Drugs

Abstract

Nitric oxide (NO) is produced during various pathophysiological conditions and its effects deleterious or beneficial depend on its location, duration of release, and the availability of other physiological reactive entities. Thus the role of NO when produced in conjunction with various drugs assumes importance. A number of studies have indicated that NO can synergize with clinically used drugs or drug candidates. These drugs include chemotherapeutics against cancer as well as antibiotics. Three strategies for enhancement of NO in conjunction with a drug are in development. First, overexpression of nitric oxide synthase, an enzyme that is responsible for synthesis of NO within cells, would result in increased NO and the effects of a drug can be studied. Second, the use of exogenous donors of NO, which are small molecules that dissociate to produce NO, are cotreated with the drug and cellular responses are determined. Lastly, conjugates of NO and the drug have been prepared and studied. Together, these strategies throw light on the possible synergistic activities of NO and drugs.