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BioMed Research International
Volume 2014, Article ID 505987, 9 pages
http://dx.doi.org/10.1155/2014/505987
Research Article

Enhanced Analgesic Properties and Reduced Ulcerogenic Effect of a Mononuclear Copper(II) Complex with Fenoprofen in Comparison to the Parent Drug: Promising Insights in the Treatment of Chronic Inflammatory Diseases

1INQUISUR, Departamento de Química, Universidad Nacional del Sur, Avenida Alem 1253, B8000CPB Bahía Blanca, Argentina
2Laboratorio de Toxicología, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000CPB Bahía Blanca, Argentina
3Centro de Investigación y Desarrollo de Fármacos (CIDEF), Facultad de Ciencias Veterinarias, Universidad Nacional de La Pampa, Calle 5 y 116, 6360 General Pico, Argentina

Received 17 February 2014; Revised 12 May 2014; Accepted 27 May 2014; Published 19 June 2014

Academic Editor: Abdel A. Abdel-Rahman

Copyright © 2014 Mariela Agotegaray et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Analgesic and ulcerogenic properties have been studied for the copper(II) coordination complex of the nonsteroidal anti-inflammatory drug Fenoprofen and imidazole [Cu(fen)2(im)2] (Cu: copper(II) ion; fen: fenoprofenate anion from Fenoprofen, im: imidazole). A therapeutic dose of 28 mg/kg was tested for [Cu(fen)2(im)2] and 21 mg/kg was employed for Fenoprofen calcium, administered by oral gavage in female mice to compare the therapeutic properties of the new entity. The acetic acid induced writhing test was employed to study visceral pain. The percentage of inhibition in writhing and stretching was 78.9% and 46.2% for the [Cu(fen)2(im)2] and Fenoprofen calcium, respectively. This result indicates that the complex could be more effective in diminishing visceral pain. The formalin test was evaluated to study the impact of the drugs over nociceptive and inflammatory pain. The complex is a more potent analgesic on inflammatory pain than the parent drug. Ulcerogenic effects were evaluated using a model of gastric lesions induced by hypothermic-restraint stress. Fenoprofen calcium salt caused an ulcer index of about 79 mm2 while the one caused by [Cu(fen)2(im)2] was 22 mm2. The complex diminished the development of gastric mucosal ulcers in comparison to the uncomplexed drug. Possible mechanisms of action related to both therapeutic properties have been discussed.