Pharmacological Evaluation of Naproxen Metal Complexes on Antinociceptive, Anxiolytic, CNS Depressant, and Hypoglycemic Properties

Abstract

Purpose. The present study was designed to investigate the antinociceptive, anxiolytic, CNS depressant, and hypoglycemic effects of the naproxen metal complexes. Methods. The antinociceptive activity was evaluated by acetic acid-induced writhing method and radiant heat tail-flick method while anxiolytic activity was evaluated by elevated plus maze model. The CNS depressant activity of naproxen metal complexes was assessed using phenobarbitone-induced sleeping time test and the hypoglycemic test was performed using oral glucose tolerance test. Results. Metal complexes significantly (P < 0.001) reduced the number of abdominal muscle contractions induced by 0.7% acetic acid solution in a dose dependent manner. At the dose of 25 mg/kg body weight p.o. copper, cobalt, and zinc complexes exhibited higher antinociceptive activity having 59.15%, 60.56%, and 57.75% of writhing inhibition, respectively, than the parent ligand naproxen (54.93%). In tail-flick test, at both doses of 25 and 50 mg/kg, the copper, cobalt, silver, and zinc complexes showed higher antinociceptive activity after 90 minutes than the parent drug naproxen. In elevated plus maze (EPM) model the cobalt and zinc complexes of naproxen showed significant anxiolytic effects in dose dependent manner, while the copper, cobalt, and zinc complexes showed significant CNS depressant and hypoglycemic activity. Conclusion. The present study demonstrated that copper, cobalt, and zinc complexes possess higher antinociceptive, anxiolytic, CNS depressant, and hypoglycemic properties than the parent ligand.

Sub-chronic toxicological studies of transition metal complexes of naproxen on sprague-dawley rats

“…In our previous paper, 22 we showed that naproxen metal complexes had better pharmacological properties than naproxen in mice. That's why we thought there might be possibilities that they could have any toxicity profiles.…”

Trinuclear silver(I) complex of non-steroidal anti-inflammatory drug naproxen: Synthesis, characterization, and in vitro cytotoxicity

“…Naproxen (Hnap), a prominent member of NSAIDs, has been mainly used in the treatment of headaches and fevers based on its analgesic and antipyretic features [25][26][27][28]. There are several papers in which silver-naproxen complexes are synthesized and their biological properties evaluated, showing better biological activities than naproxen [29][30][31][32]. The synthesis of novel silver(I)-naproxen complexes means designing of a new chemotherapeutic agent, and therefore, significant efforts should be made to synthesize the complexes and investigate their cytotoxic activity against both different types of cancer cell lines and normal cells.…”