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4-甲氧羰基-4-N-丙酰苯胺基哌啶1位衍生物的合成及其镇痛作用 总被引:2,自引:0,他引:2
本文报道了一系列N-[-1(2-苯乙基-4-甲氧羰基-4-哌啶基]-N-丙酰苯胺(4-甲氧羰基芬太尼)哌啶环1位取代衍生物的合成及其镇痛活性;讨论了结构与镇痛活性之间的关系。药理试验结果表明,大部分化合物具有典型的吗啡样镇痛活性,是一类作用极强的麻醉性镇痛剂。特别是哌啶环1位β-苯环被取代乙烯基替代的化合物具有相当或接近子母体化合物的镇痛活性。其代表物1321的镇痛活性(ED_(50)=0.005mg/kg ip,小鼠,热板法)略强于4-甲氧羰基芬太尼(ED_(50)=0.0063 mg/kg)。 相似文献
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Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle 总被引:2,自引:0,他引:2
Kramer HF Witczak CA Fujii N Jessen N Taylor EB Arnolds DE Sakamoto K Hirshman MF Goodyear LJ 《Diabetes》2006,55(7):2067-2076
Insulin and contraction increase GLUT4 translocation in skeletal muscle via distinct signaling mechanisms. Akt substrate of 160 kDa (AS160) mediates insulin-stimulated GLUT4 translocation in L6 myotubes, presumably through activation of Akt. Using in vivo, in vitro, and in situ methods, insulin, contraction, and the AMP-activated protein kinase (AMPK) activator AICAR all increased AS160 phosphorylation in mouse skeletal muscle. Insulin-stimulated AS160 phosphorylation was fully blunted by wortmannin in vitro and in Akt2 knockout (KO) mice in vivo. In contrast, contraction-stimulated AS160 phosphorylation was only partially decreased by wortmannin and unaffected in Akt2 KO mice, suggesting additional regulatory mechanisms. To determine if AMPK mediates AS160 signaling, we used AMPK alpha2-inactive (alpha2i) transgenic mice. AICAR-stimulated AS160 phosphorylation was fully inhibited, whereas contraction-stimulated AS160 phosphorylation was partially reduced in the AMPK alpha2i transgenic mice. Combined AMPK alpha2 and Akt inhibition by wortmannin treatment of AMPK alpha2 transgenic mice did not fully ablate contraction-stimulated AS160 phosphorylation. Maximal insulin, together with either AICAR or contraction, increased AS160 phosphorylation in an additive manner. In conclusion, AS160 may be a point of convergence linking insulin, contraction, and AICAR signaling. While Akt and AMPK alpha2 activities are essential for AS160 phosphorylation by insulin and AICAR, respectively, neither kinase is indispensable for the entire effects of contraction on AS160 phosphorylation. 相似文献
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L.P. Rodrigues D. Iglesias F.C. Nicola D. Steffens L. Valentim A. Witczak G. Zanatta M. Achaval P. Pranke C.A. Netto 《Brazilian journal of medical and biological research》2012,45(1):49-57
Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 106 cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 106 cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation. 相似文献
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Artificial feeding of infants is applied in situations when breastfeeding is impossible for various reasons. Such feeding is based on modified cow's milk made similar in composition to human milk. The aim of this study was to examine the content of Mg, Ca, K and Na in infant and follow-on formulae. The study also evaluated how the formulae satisfy the demand for these minerals in children of different age groups. The study has revealed that an excess supply of the minerals occurred in infant formulae (from 0 to 6 months) comparing to the recommended values (AI, EAR, RDA). 相似文献
37.
目的 :研究硝苯吡啶以及硝苯吡啶与格列本脲合用对空腹大鼠和肾上腺素诱发高血糖大鼠血糖水平的影响。方法 :本实验采用葡萄糖氧化酶法测定血糖含量。结果 :硝苯吡啶 2 .5mg/kgig使空腹大鼠血糖水平显著升高(P <0 .0 1 ) ,并加重肾上腺素诱发的高血糖反应。而硝苯吡啶与降糖药格列本脲 0 .9mg/kg合用时不影响空腹大鼠的血糖水平 ,硝苯吡啶对肾上腺素诱发高血糖大鼠灌胃格列本脲后的降血糖作用亦无明显影响。结论 :尽管硝苯吡啶对空腹大鼠以及肾上腺素诱发高血糖大鼠有显著升高血糖的作用 ,但对格列本脲的降血糖作用无明显不良影响 相似文献
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After congenital heart defects neural tube defects (NTDs) is the second most prevalent congenital malformation among birth defects. The average rate of isolated NTDs is 1.4-2.0 per 1000 live births worldwide. The etiology of isolated (nonsyndromic) NTDs is believed to be the result of a combination of genetic predisposition and environmental factors. Over 80 genes believed to be engaged in the neurulations have been identified during the investigation and research of the mouse models. Despite exhaustive research efforts, now spanning several decades, little is known about the actual genetic mechanisms governing the primary events involved in neural tube closure (NTC). 相似文献
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