Soft drugs in anesthesia: remifentanil as prototype to modern anesthetic drug development.

Abstract

The unique demands of modern anesthesia practice require that medications be effective, well tolerated, and efficient. These attributes are increasingly achieved with the soft drug approach, wherein novel active compounds are specifically designed to be susceptible to rapid biotransformation to inactive metabolites. The present review summarizes the historical background and recent trends in soft drug development in anesthesiology. Soft drug development programs for propranadid, etomidate, and benzodiazepine analogues have been undertaken in recent years. Although all three drugs advanced into human trials, neuro-excitatory adverse effects hampered the propranadid and etomidate analogue projects. Remimazolam, the soft benzodiazepine analogue, is at an advanced stage of development, having already received regulatory approval or review in several countries. With succinylcholine as the historical forerunner and remifentanil as the modern prototype, the soft drug paradigm continues to hold promise for the future of anesthesia drug development.