Investigational drugs targeting the prostaglandin E2 signaling pathway for the treatment of inflammatory pain.

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAID) are the most commonly used drugs for the treatment of pain, inflammation and fever. Although they are effective for a huge number of users, their analgesic properties are not sufficient for several patients and the occurrence of side effects still constitutes a big challenge during long term therapy. Areas covered: This review gives an overview about the first and second generations of NSAIDs (COX1/2 non-selective, COX-2 selective), and their main side effects which gave still an urgent need for safer drugs and for the establishment of novel treatment strategies (improved safety, tolerability, patient convenience). The current developments of a possible third generation NSAID class comprise changes in the formulation of already approved drugs, combination therapies, dual cyclooxygenase-lipoxygenase inhibitors, NO- and H2S-releasing NSAIDs, prostaglandin synthase inhibitors and EP receptor modulators, respectively. Literature search has been done with PubMed NCBI. Expert opinion: Currently, there is no newly developed drug that is superior to the already approved selective and non-selective NSAIDs. Several novel approaches show promising analgesic efficacy but side effects are still an important problem. Solutions might be constituted by combination therapies allowing administration of lower drug doses or by individualized therapies targeting molecules apart from COX, respectively.