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排序方式: 共有62条查询结果,搜索用时 15 毫秒
1.
Chakraborty Bhaswat S. Sardessai Manik S. Jaworski Theodore J. Midha Kamal K. Hawes Edward M. 《Pharmaceutical research》1987,4(3):207-213
For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[l-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten–protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized. 相似文献
2.
Summary The blood chemistry and clinical pharmacokinetics of thioridazine and its metabolites, side-chain sulphoxide, side-chain sulphone and ring sulphoxide, were studied in 31 alcoholics and were compared with values in 17 thioridazine-treated controls without alcoholism. Pathological blood chemistry values, including abnormal liver function and protein concentrations, were common among the alcoholics. In relation to dosage, the majority had a low serum concentration of thioridazine and at a given concentration of thioridazine they had high serum concentrations of its metabolites. Positive intercorrelations were found between pathological liver function tests, prolonged serum half-life and increased serum concentration of thioridazine. The free fractions of thioridazine, side-chain sulphoxide and ring sulphoxide were significantly higher and those of the side-chain sulphone lower in the alcoholics than in the controls. The free fractions of side-chain and ring sulphoxide were significantly increased in patients with a low concentration of 1-acid glycoprotein. 相似文献
3.
Summary Plasma-levels of thioridazine, mesoridazine, sulphoridazine and two other metabolites were determined in ten older chronic psychotic patients on thioridazine therapy. The plasma-level before the morning dose of thioridazine was the most reliable parameter for clinical studies. An intra-individual relationship between lower doses of thioridazine and plasma-levels was found. The percentage contribution of psychoactive compounds to the total sum of thioridazine plus metabolites ranged from 43–74%. The mean early disappearance half-life of thioridazine was 5 hours, and its mean late disapperance half-life was 26 hours. 相似文献
4.
Adam J. Prus Scott D. Philibin Alan L. Pehrson Chad L. Stephens Rhiannon N. Cooper Laura E. Wise Joseph H. Porter 《Drug development research》2005,64(1):55-65
Clozapine (CLZ) drug discrimination is used as a preclinical model to evaluate compounds for putative atypical antipsychotic properties. In rats, a 1.25 mg/kg CLZ training dose appears to have greater pharmacological specificity for atypical antipsychotic drugs than the traditional 5.0 mg/kg CLZ training dose; however, methodological differences among studies have precluded a direct comparison between these training doses. In the present study, rats were trained to discriminate a 5.0 mg/kg CLZ dose from vehicle in a two‐choice drug discrimination task using methods similar to those in a previous study from our laboratory that used a 1.25 mg/kg CLZ training dose. Clozapine produced full substitution (≥80% CLZ‐lever responding) for itself at the training dose (5.0 mg/kg). The atypical antipsychotics olanzapine, quetiapine, and ziprasidone also produced full substitution for 5.0 mg/kg CLZ, whereas the atypical antipsychotics risperidone and sertindole produced partial substitution (≥60% CLZ‐lever responding). The typical antipsychotic, thioridazine, produced full substitution for the 5.0 mg/kg CLZ training dose, but the typical antipsychotics chlorpromazine, fluphenazine, and haloperidol failed to substitute for clozapine. In a subgroup of 1.25 mg/kg CLZ‐trained rats, ziprasidone produced strong partial substitution (73.0 % CLZ‐lever responding) for the 1.25 mg/kg CLZ training dose. Based on these findings, some atypical antipsychotic drugs (i.e., quetiapine and ziprasidone) produce full substitution only for the 5.0 mg/kg CLZ training dose, whereas other atypical antipsychotic drugs (i.e., sertindole and risperidone) produce full substitution only for the 1.25 mg/kg CLZ training dose. Thus, both of these training doses are important for the screening of putative atypical antipsychotic drugs with the clozapine drug discrimination assay. Drug Dev. Res. 64:55–65, 2005. © 2005 Wiley‐Liss, Inc. 相似文献
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目的研究硫利达嗪对结肠癌SW480细胞增殖及凋亡的影响。方法应用5~30 μmol/L硫利达嗪处理SW480细胞,MTT
法检测细胞增殖抑制率;Hoechst33342 细胞核染色法观察细胞凋亡的形态学改变;流式细胞仪检测细胞凋亡率、细胞周期;
RT-qPCR分析PDCD4、c-MYC、BCL2、CCND1、CASPASE3、PARP1、CDK4、EIF4A基因表达水平;Western blotting 检测AKT、
p-AKT、PDCD4蛋白表达水平。结果MTT结果表明硫利达嗪抑制SW480细胞的增殖,硫利达嗪处理细胞后出现核固缩、染色
质凝集和核碎片化等典型的细胞凋亡特征;流式检测表明硫利达嗪诱导G0/G1期阻滞,细胞凋亡增加。RT-PCR结果表明硫利达
嗪处理细胞后PDCD4表达上调,CCND1、CDK4、c-MYC、BCL2、CASPASE3、PARP1和EIF4A表达下调。免疫印迹分析结果显
示PDCD4蛋白表达上调,p-AKT蛋白表达下调。结论硫利达嗪能够抑制人结肠癌SW480细胞的增殖,并诱导其凋亡,其机制
可能与抑制PI3K/AKT信号通路导致PDCD4表达水平升高有关。
相似文献
法检测细胞增殖抑制率;Hoechst33342 细胞核染色法观察细胞凋亡的形态学改变;流式细胞仪检测细胞凋亡率、细胞周期;
RT-qPCR分析PDCD4、c-MYC、BCL2、CCND1、CASPASE3、PARP1、CDK4、EIF4A基因表达水平;Western blotting 检测AKT、
p-AKT、PDCD4蛋白表达水平。结果MTT结果表明硫利达嗪抑制SW480细胞的增殖,硫利达嗪处理细胞后出现核固缩、染色
质凝集和核碎片化等典型的细胞凋亡特征;流式检测表明硫利达嗪诱导G0/G1期阻滞,细胞凋亡增加。RT-PCR结果表明硫利达
嗪处理细胞后PDCD4表达上调,CCND1、CDK4、c-MYC、BCL2、CASPASE3、PARP1和EIF4A表达下调。免疫印迹分析结果显
示PDCD4蛋白表达上调,p-AKT蛋白表达下调。结论硫利达嗪能够抑制人结肠癌SW480细胞的增殖,并诱导其凋亡,其机制
可能与抑制PI3K/AKT信号通路导致PDCD4表达水平升高有关。
相似文献
7.
8.
A. Harenko I. Alanen S. Elovaara S. Ginstrm U. Hagert M. Savijrvi A. Yli-kerttula K. Elgen 《International journal of geriatric psychiatry》1992,7(5):369-375
A four-week double-blind study of zuclopenthixol and thioridazine in 64 elderly patients presenting with hostility or restlessness has been carried out in five Finnish mental hospitals. The ages of the patients in the two groups ranged from 64 to 97 years. The initial daily dose was 2–6 mg zuclopenthixol or 20–60 mg thioridazine. In week 4 the mean daily dose was 6.8 mg zuclopenthixol and 62 mg thioridazine. AFter one week of treatment the severity of illness was reduced significantly in the zuclopenthixol group and in both groups after two and four weeks. The key symptom hostility showed significant improvement in both treatment groups after only one week of treatment. The other key symptom restlessness was also significantly improved in both groups. The only significant difference between the groups was a better effect on sleep disturbance with zuclopenthixol. Few side-effects were recorded in either group, and no serious effects on cardiovascular function were found. The study indicates that both zuclopenthixol and thioridazine are effective drugs in the treatment of elderly patients with symptoms such as hostility, aggressiveness and restlessness. 相似文献
9.
The contrasting effects of neuroleptics on transmitter release from the nucleus accumbens and corpus striatum 总被引:3,自引:0,他引:3
The effects of haloperidol, chlorpromazine and clozapine on transmitter release have been studied by measuring the simultaneous release of dopamine and acetylcholine from tissue slices of nucleus accumbens and striatum in vitro following in vivo drug application, either a single dose or daily for periods of up to 25 days. In the striatum, both single and chronic injections of haloperidol (1 and 2 mg. kg-1) caused a large and significant enhancement (up to 83%) of the K+-evoked release of [3H]acetylcholine synthesized from [3H]choline. In contrast, in the nucleus accumbens, the K+-evoked release of [3H]acetylcholine was not significantly affected by neuroleptics when compared with the controls which received injection of vehicle. Clozapine (50 mg.kg-1) also enhanced the K+-evoked release of [3H]acetylcholine relative to the resting release but the effect was smaller than that with haloperidol or chlorpromazine. The evoked release of preloaded [14C]dopamine from either nucleus accumbens or striatum was unaffected by treatment with haloperidol. However, chlorpromazine (25 mg.kg-1) and clozapine (50 mg.kg-1) significantly enhanced the evoked release of preloaded [14C]dopamine from tissue slices of striatum. A similar but reduced effect of enhancing release was also seen in the nucleus accumbens in response to chlorpromazine. In support of these results, dopamine itself applied in vitro induced an opposite effect to that of the neuroleptics. Thus in the striatum, dopamine (4 x 10(-4) M) markedly reduced the release of [3H]acetylcholine (45%). A smaller inhibition was also seen in the nucleus accumbens (25%). 相似文献
10.
The effects of promazine and thioridazine on hypotonic haemolysis of human erythrocytes are compared with their effect on Na+-K+-ATPase of washed human erythrocyte ghosts. Promazine (5 × 10-5 - 5 × 10-4 M) and thioridazine (10-5 - 10-4 M) stabilize erythrocytes against hypotonic haemolysis, but have lytic effects at higher concentrations. Both drugs inhibit Na+-K+-ATPase of erythrocyte membranes. This inhibition is slight at drug concentrations which have a membrane-stabilizing action, but is complete and irreversible at lytic concentrations of the drugs. Promazine and thioridazine also inhibit Na+-K+-ATPase in a membrane fraction prepared from rat hearts. The relative order of potency of the two drugs in this respect does not reflect their relative potency as general cardiac depressants. It is concluded that Na+-K+-ATPase is not a primary target for the action of promazine and thioridazine in the rat heart. It is suggested that inhibition of Na+-K+-ATPase by these agents is secondary to more general alterations of the physical properties of the cell membrane. 相似文献