Synthesis of Novel Esters of Mefenamic Acid with Pronounced Anti-nociceptive Effects and a Proposed Activity on GABA, Opioid and Glutamate Receptors.

Abstract Background Mefenamic acid (MFA), a commonly prescribed non-steroidal anti-inflammatory drug (NSAID), possesses a greater risk of dose-related central nervous system (CNS) toxicity than other NSAIDs. In this study, α-tocopherol and α-tocopherol acetate were selected as prodrug moieties for MFA in an attempt to reduce the CNS toxicity and enhance the therapeutic efficacy. Method α-tocopherol monoester of MFA (TMMA) and α-tocopherol di-ester of MFA (TDMA) were synthesized by esterification reaction and were subjected to various in vivo characterizations. Results Masking of the carboxylate group of MFA with the proposed pro-moieties significantly (p Conclusion Masking the carboxylate moiety of MFA by α-tocopherol and α-tocopherol acetate has a great potential for reducing CNS toxicity, enhancing the therapeutic efficacy and altering the mode of anti-nociceptive action.