Abraham Nudelman* Pages 4283 - 4339 ( 57 )
This review encapsulates an extensive variety of substances identified as mutual prodrugs or codrugs, wherein two, or sometimes three, biologically active moieties are linked using an assortment of metabolically unstable bridging entities. Following the administration of the mutual prodrugs, these undergo a bridge cleavage releasing the active molecules, which then elicit their respective biological effects. In some cases, the released drugs act synergistically, other times the biological activity of only one of the drugs is elicited, and in such cases, the accompanying drug serves only as a carrier, which may have an affinity to the desired receptor. The most promising results are commonly observed when the two released drugs are efficacious at similar concentrations and particularly when the two drugs are effective against similar diseases. For instance, the best results are observed, when two analgesics, two anticancer agents, two drugs for the treatment of cardiac conditions, etc., are the substances comprising the codrug. Mutual prodrugs/ codrugs described herein have been reported, primarily since the year 2000, as potential drugs for use against a plethora of diseases including pain, inflammation, cancer, bacterial infections, sickle cell anemia, Alzheimer’s disease, and others.
Mutual prodrugs, codrugs, drug synergism, biological activity, linking bridges, metabolic activation.