RESUMO
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 mm(2) while the one caused by [Cu(fen)2(im)2] was 22 mm(2). 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.
Assuntos
Analgésicos/uso terapêutico , Complexos de Coordenação/uso terapêutico , Cobre/uso terapêutico , Fenoprofeno/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Úlcera Gástrica/tratamento farmacológico , Analgésicos/química , Analgésicos/farmacologia , Animais , Doença Crônica , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Cobre/farmacologia , Feminino , Fenoprofeno/química , Fenoprofeno/farmacologia , Doenças Inflamatórias Intestinais/patologia , Camundongos , Úlcera Gástrica/patologiaRESUMO
El presente trabajo tiene como objetivo describir las características farmacocinéticas, metabólicas y toxicológicas de los ácidos asimétricos aril-2-propiónicos y mostrar la importante variabilidad inter-especies existentes. Además se explican las derivaciones metabólicas del proceso de inversión quiral (camino metabólico de crucial importancia para estos compuestos) y las consecuencias toxicológicas relacionadas con su naturaleza quiral
Assuntos
Humanos , Propionatos/química , Anti-Inflamatórios não Esteroides/toxicidade , Fenoprofeno/toxicidade , Cetoprofeno/toxicidade , Conformação Molecular , Albumina Sérica , Fenoprofeno/metabolismo , Fenoprofeno/farmacologia , Cetoprofeno/metabolismo , Cetoprofeno/farmacologia , Oxigenases/farmacologia , Prostaglandinas/biossínteseRESUMO
El presente trabajo tiene como objetivo describir las características farmacocinéticas, metabólicas y toxicológicas de los ácidos asimétricos aril-2-propiónicos y mostrar la importante variabilidad inter-especies existentes. Además se explican las derivaciones metabólicas del proceso de inversión quiral (camino metabólico de crucial importancia para estos compuestos) y las consecuencias toxicológicas relacionadas con su naturaleza quiral (AU)