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991.
Yves Claustre Danielle De Peretti Philippe Brun Christiane Gueudet Nathalie Allouard Richard Alonso Jo?lle Lourdelet André Oblin Gabrielle Damoiseau Dominique Fran?on Marie-Fran?oise Suaud-Chagny Régis Steinberg Mireille Sevrin Hans Schoemaker Pascal George Philippe Soubrié Bernard Scatton 《Neuropsychopharmacology》2003,28(12):2064-2076
SSR181507 ((3-exo)-8-benzoyl-N-[[(2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo[3.2.1]octane-3-methanamine monohydrochloride) is a novel tropanemethanamine benzodioxane derivative that possesses high and selective affinities for D2-like and 5-HT(1A) receptors (K(I)=0.8, 0.2, and 0.2 nM for human D(2), D(3), and 5-HT(1A), respectively). In vivo, SSR181507 inhibited [(3)H]raclopride binding to D(2) receptors in the rat (ID(50)=0.9 and 1 mg/kg, i.p. in limbic system and striatum, respectively). It displayed D(2) antagonist and 5-HT(1A) agonist properties in the same concentration range in vitro (IC(50)=5.3 nM and EC(50)=2.3 nM, respectively, in the GTPgammaS model) and in the same dose range in vivo (ED(50)=1.6 and 0.7 mg/kg, i.p. on striatal DA and 5-HT synthesis, respectively, and 0.03-0.3 mg/kg, i.v. on dorsal raphe nucleus firing rate). It selectively enhanced Fos immunoreactivity in mesocorticolimbic areas as compared to the striatum. This regional selectivity was confirmed in electrophysiological studies where SSR181507, given acutely (0.1-3 mg/kg, i.p.) or chronically (3 mg/kg, i.p., o.d., 22 days), increased or decreased, respectively, the number of spontaneous active DA cells in the ventral tegmental area, but not in the substantia nigra. Moreover, SSR181507 increased both basal and phasic DA efflux (as assessed by microdialysis and electrochemistry) in the medial prefrontal cortex and nucleus accumbens, but not in the striatum. This study shows that the combination of D(2) receptor antagonism and 5-HT(1A) agonism, in the same dose range, confers on SSR181507 a unique neurochemical and electrophysiological profile and suggests the potential of this compound for the treatment of the main dimensions of schizophrenia. 相似文献
992.
Gunter Kenis Harry Steinbusch Marc De Baets Michael Maes 《European neuropsychopharmacology》2003,13(1):53-56
This study examines the effects of paroxetine and imipramine on intracellular concentrations of cyclic adenosine monophosphate (cAMP) in human peripheral blood mononuclear cells. It was found that imipramine and paroxetine had no effect on basal cAMP-levels. Stimulation with lipopolysaccharides and phytohaemagglutinin increased intracellular cAMP concentrations. However, pre-incubation with imipramine or paroxetine, did not influence this increase. These data do not support the hypothesis that cAMP may be related to the in vitro anti-inflammatory effects of antidepressants. 相似文献
993.
Fernanda B Nunes Cássio M Graziottin José Carlos F Alves Filho Adroaldo Lunardelli Melissa G S Pires Paulo H W?chter Jarbas R De Oliveira 《Pharmacological research》2003,47(1):35-41
Tissue lesion mechanisms provoked by sepsis include the infectious process, inflammation, and cellular energy deficit. We chose to test fructose-1,6-bisphosphate (FBP) because of its possible anti-inflammatory and antimicrobial actions. Wistar rats were used and divided into three experimental groups: a control group (n=10), in which a capsule was introduced into the peritoneum of the animals; a septic group (n=10), in which a capsule containing non-sterile fecal matter was introduced together with Escherichia coli (1.5 x 10(9)CFU); and a septic group treated with FBP 500 mg/kg (n=10). The blood cell tests revealed that levels of leukocytes increased significantly in the septic group when compared to both the septic group treated with FBP and the control group. The blood cultures were 100% positive in both the septic group and the septic group treated with bisphosphorylated sugar. The antibiogram only revealed an inhibitory halo in the case of the antibiotic ampicillin, there was no such indication for FBP. The anti-inflammatory power of FBP remained at 60% for 5 h in the rats that received the carrageenan injection. What is more, the sugar reduced the levels of ionic calcium in relation to the control group. This data proves the validity of using FBP in the treatment of sepsis, possibly due to its anti-inflammatory rather than antimicrobial action. 相似文献
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995.
氟哌啶醇对人红白血病耐多柔比星细胞株多药耐药性的逆转及其机制 总被引:1,自引:0,他引:1
目的 从临床常用药物中探寻逆转肿瘤耐药性的活性物质。方法 应用MTT法测定不同浓度Hal处理的瘤细胞对 0~ 2 0 μmol·L- 1多柔比星 (Dox)的敏感性的影响。RT PCR法分析 12 .5 μmol·L- 1氟哌啶醇 (Hal)处理后多药耐药基因 (MDR1) ,多药耐药相关蛋白 (MRP)和谷胱甘肽S转移酶Pi(GSTπ)mRNA表达的变化。通过流式细胞术观察 0 ,6 .2 5 ,12 .5 ,2 5 μmol·L- 1Hal对细胞内药物蓄积和细胞周期进程的影响。结果 Hal对K5 6 2 /Dox的耐药性具有明显的逆转作用。在 12 .5 ,6 .2 5及 3.12 5 μmol·L- 1时的逆转倍数分别为 8.35 ,4 .2 1及 2 .16。用 12 .5μmol·L- 1Hal处理后 ,MDR1及MRP的mRNA表达水平均呈现时间依赖性明显降低 ,分别较原水平下降76 .3%及 6 4.6 %。药后d 2GSTπmRNA表达下降6 6 .1% ,于d 3回升。Hal处理细胞lh后 ,Dox在细胞内蓄积量明显增加 ,并呈浓度依赖性 ;此外 ,Hal可明显增强Dox对K5 6 2 /Dox细胞的G2 /M阻滞作用 ,12 .5 μmol·L- 1浓度可以使 5 μmol·L- 1Dox的G2 /M阻断由单独应用时的 9.9%± 4 .3%增加到2 3.4 %± 3.0 %。结论 Hal具有较强的逆转K5 6 2 /Dox细胞MDR的作用 ,其逆转机制为多种途径 ,包括相关基因mRNA的表达下调 ,增加细胞内药物蓄积 ,增强Dox对K5 6 2 /Dox在G2 相似文献
996.
Berti M Albertin A Casati A Palmisano S Municino G da Gama Malcher M De Ponti A 《Minerva anestesiologica》2000,66(7-8):549-554
BACKGROUND: This prospective, randomized study was conducted to evaluate the quality of postoperative pain relief when using dexketoprofen, ketoprofen, or paracetamol after outpatient knee arthroscopy. METHODS: Without premedication, 45 ASA physical status I-II patients undergoing elective outpatient knee arthroscopy with combined sciatic-femoral nerve block, were randomly allocated to receive either 25 mg oral dexketoprofen (n = 15), 50 mg oral ketoprofen (n = 15), or 500 mg oral paracetamol (n = 15) before block placement. After completion of surgery the same pain medication was given according to standard protocols, while 50 mg oral tramadol were allowed as rescue analgesic if required by the patient. After standard discharge criteria had been fulfilled, patients were discharged from the day-surgery unit, while a telephone follow-up was performed the day after surgery using standard questionnaires evaluating the quality of pain relief during the first 24 hours after surgery. Total consumption of rescue tramadol, maximum pain complained of after hospital discharge, as well as the visual analogue scale of pain measured at hospital discharge were assessed by an independent trained observer. RESULTS: No differences in anthropometric variables, duration of surgical procedure, and fulfillment of discharge criteria were observed between the three groups. The degree of pain measured at rest at hospital discharge was similar in the three groups, while the VAS measured during motion was higher in patients receiving paracetamol (24 +/- 2.5 mm) than in those patients treated with dexketoprofen (13 +/- 6 mm) or ketoprofen (17 +/- 5 mm) (p = 0.016). Two patients (one in ketoprofen group and one in paracetamol group) required rescue tramadol after hospital discharge; however, no differences in maximum pain complained of after surgery or patient acceptance were observed between groups. CONCLUSIONS: This prospective, randomized study demonstrated that in outpatients receiving arthroscopic knee surgery, the use of 75 mg/day dexketoprofen was as effective and safe as 150 mg/day racemate ketoprofen, with a better pain relief during motion compared to 2 g/day paracetamol when patients were discharged from the day-surgery unit. 相似文献
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