RESUMEN
The thermal, physical, and morphological properties of diphenhydraminium ibuprofenate ([DIP][IBU]) adsorbed onto mesoporous silica (SiO2-60â¯Å and SiO2-90â¯Å) from solution were determined. The thermal, physical, and morphological properties of [DIP][IBU] supported on silica were determined. The adsorption of [DIP][IBU] on the pores and surface of silica was proven by N2 adsorption/desorption isotherms. Additionally, release profiles were determined for all systems, and the antinociceptive activity of neat [DIP][IBU] and [DIP][IBU] supported on silica were determined. The interaction of [DIP][IBU] and silica was dependent on pore size, with the formation of a [DIP][IBU] monolayer on SiO2-60 and a multilayer on SiO2-90. The release profile was sustained and slow and dependent on the pore size of the silica, in which the smaller the pore size, the faster the release. The nociceptive evaluation showed that [DIP][IBU] presents a greater (99.21⯱â¯0.85%) antinociceptive effect than the ibuprofen (46⯱â¯4.3%). Additionally, [DIP][IBU] on SiO2-60 (90⯱â¯5.8%) had a greater antinociceptive effect than on SiO2-90 (73⯱â¯13.2%), which indicates that in vivo tests are in accordance with the in vitro experiments.
Asunto(s)
Analgésicos , Ibuprofeno , Dolor/tratamiento farmacológico , Dióxido de Silicio , Analgésicos/química , Analgésicos/farmacocinética , Analgésicos/farmacología , Animales , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Evaluación Preclínica de Medicamentos , Ibuprofeno/análogos & derivados , Ibuprofeno/química , Ibuprofeno/farmacocinética , Ibuprofeno/farmacología , Masculino , Ratones , Dolor/metabolismo , Dolor/fisiopatología , Porosidad , Dióxido de Silicio/química , Dióxido de Silicio/farmacocinética , Dióxido de Silicio/farmacologíaRESUMEN
Herein we report the synthesis of twelve 2,5-substituted 4-(trifluoromethyl)-spirochromeno[4,3-d]pyrimidines (7-10), as well as an evaluation of their analgesic effect in a mouse pain model. The nine new chromeno[4,3-d]pyrimidines (7-9) were synthesized from the cyclocondensation reactions of three 2,2,2-trifluoro-1-(4-methoxyspiro[chromene-2,1'-cycloalkane]-3-yl)ethanones (3) containing 5-, 6- and 7-membered spirocycloalkanes, with some well-known amidine salts (4-6) [NH2CR(NH)]-in which R=Me, Ph, and NH2-at yields of 60-95%. Subsequently, three new 2-(pyrrol-1-yl)-4-(trifluoromethyl)-chromeno[4,3-d]pyrimidines (10) were obtained through a Clauson-Kaas reaction between the respective 2-(amino)-4-(trifluoromethyl)-chromeno[4,3-d]pyrimidines (9) and 2,5-dimethoxy-tetrahydrofuran. The analgesic evaluation showed that these 4-(trifluoromethyl)chromeno[4,3-d]pyrimidines (100mg/kg, p.o.) and Ketoprofen (100mg/kg, p.o.) significantly reduced capsaicin-induced spontaneous nociception. Moreover, the 2-pyrrolyl-spirocyclohexane derivative 10b (100 and 300mg/kg, p.o.) had an anti-allodynic effect comparable to Ketoprofen (100 and 300mg/kg, p.o.) in the arthritic pain model, without causing locomotor alterations in the mice. These results suggest that the compound 10b is a promising molecule for new analgesic drugs in the treatment of pathological pain, such as in arthritis.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Benzopiranos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Dolor/tratamiento farmacológico , Pirimidinas/uso terapéutico , Compuestos de Espiro/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/síntesis química , Artritis/inducido químicamente , Artritis/tratamiento farmacológico , Artritis/fisiopatología , Benzopiranos/administración & dosificación , Benzopiranos/síntesis química , Capsaicina , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/síntesis química , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/fisiopatología , Cetoprofeno/administración & dosificación , Cetoprofeno/farmacología , Ratones , Nocicepción/efectos de los fármacos , Dolor/inducido químicamente , Dolor/fisiopatología , Pirimidinas/administración & dosificación , Pirimidinas/síntesis química , Compuestos de Espiro/administración & dosificación , Compuestos de Espiro/síntesis químicaRESUMEN
OBJECTIVES: The study was aimed at investigating the effects of osteopenia and calcium supplementation on antioxidant enzyme activities (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) in postmenopausal women. DESIGN AND METHODS: Postmenopausal women (n=75) were divided into two groups, control (no bone disease) and osteopenia, according to their bone mineral density. Each group was still divided into calcium-supplemented and nonsupplemented sub-groups. Antioxidant enzyme activities were determined in whole blood using spectrophotometric methods. RESULTS: CAT and SOD activities were not different among the studied groups. However, GPx activity was significantly higher in osteopenia groups as compared to control groups. Calcium supplementation had no effect on the parameters evaluated. Bone mineral density was negatively correlated with GPx activity (p<0.05). CONCLUSIONS: Increased GPx activity could be interpreted as a defense response to counteract the overproduction of reactive oxygen species in women with osteopenia, and this effect was not prevented by calcium supplementation.