The sequence of events associated with the discovery and development of non-steroidal anti-inflammatory drugs (NSAID) remains in complete opposition against the modern model of research and development program for new drug candidates. In this case, it was the drug that appeared first and then its mechanism of action was described. In the previous part of this article the history of discovery of non-steroidal anti-inflammatory drugs was described covering the period from ancient times until 1960s. In this part we will discuss the historical aspects of the last 60 years, related to the discovery of the pathomechanism of pain and pharmacodynamic properties of non-steroidal anti-inflammatory drugs, which contributed to the development of selective inhibitors of cyclooxygenase-2 – coxibs. The story behind these compounds has been defined by great expectations and unexpected failure, which obviously has prompted the need for further development in the field of pharmacotherapy of pain and inflammatory conditions.

Keywords: cyclooxygenase, NSAID, coxibs, cardiotoxicity.