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81.
目的 :观察丙咪嗪与尼莫地平并用对心血管功能的影响 ,为两药配伍应用提供实验依据。方法 :采用 SMU P-PC型生物信号处理系统和心电图机 ,测定丙咪嗪、尼莫地平及两者并用时家兔血压和心电图变化。结果 :尼莫地平组血压、心电图无明显变化 ;丙咪嗪组血压下降 ,与给药前比较差异显著 (P<0 .0 5 ) ,16 %出现室性早搏 ;丙咪嗪与尼莫地平半量并用组 ,血压下降幅度小 ,与给药前比较无统计学意义 (P>0 .0 5 ) ,无室性早搏。全量并用组血压下降及心电图变化与丙咪嗪单用相似。结论 :尼莫地平对丙咪嗪的心血管副作用无协同作用 ,利用两药在抗抑郁方面的协同作用治疗抑郁症时 ,适当减小丙咪嗪的用药剂量 ,可在一定程度上减轻丙咪嗪对心血管功能的不良反应。 相似文献
82.
Miklos Palkovits Rita Raisman Michael Briley Salomon Z. Langer 《Brain research》1981,210(1-2):493-498
[3H]imipramine binding was measured in 23 microdissected areas of the rat brain and compared to published values for the endogenous levels of serotonin, noradrenaline and dopamine in the same areas.
The density of [3H]imipramine binding sites appears to be highly correlated with the distribution of endogenous serotonin especially where the serotonin is located mainly in nerve terminals. A weak but still significant correlation also exists with the distribution of endogenous noradrenaline whereas no such correlation could be detected for endogenous dopamine. 相似文献
83.
以丙咪嗪为探针药物,采用体内代谢的方法研究甘草和五味子对大鼠肝微粒体细胞色素P450(CYP450)的影响。将大鼠随机分为甘草、五味子、生理盐水(空白对照)、苯巴比妥(阳性对照)组,测定各组CYP450的质量摩尔浓度。并于末次给药次日,进行大鼠右侧颈静脉插管手术。手术后第2天静脉给予丙咪嗪,定点取血,HPLC法测定丙咪嗪体内代谢变化。结果:各中草药组CYP450的水平均被显著诱导,丙咪嗪的体内代谢发生了明显改变。研究显示甘草和五味子对大鼠CYP450有诱导作用,且与剂量及诱导时间有关;被诱导的大鼠丙咪嗪的体内代谢加快,甘草和五味子与丙咪嗪合用时药代动力学发生改变。 相似文献
84.
We have used the recent tritium-sensitive film method of quantitative autoradiography to localize in rat brain high-affinity binding sites for nitroimipramine (NI), a long-lasting inhibitor of serotonin (5-HT) transport in platlets. The distribution of NI binding sites in rat brain closely parallels the location of 5-HT terminals. There are high concentrations of binding sites in the dorsal and medial raphe nuclei, the basal portion of the mammilary nuclei, the medial forebrain bundle, the olfactory tubercule and the posterior basal nucleus of the amygdala. The association of [3H]NI binding sites with regions having a high content of 5-HT supports the notion that the high-affinity binding site for [3H]NI corresponding to some aspect of the presynaptic uptake site for 5-HT. 相似文献
85.
The effects of single doses of 50 mg of viloxazine, 100 mg of viloxazine, 50 mg of imipramine, and placebo given alone and in combination with alcohol on perceptual-motor performance potentially related to driving were studied in eight normal subjects. The study design permitted testing of visual reaction time, pursuit rotor performance, and depth perception when blood levels of the active drugs and alcohol were at or near peak. Analyses revealed that the effects of alcohol increased visual reaction time and decreased pursuit rotor performance. None of the drugs produced statistically significant changes on any of the measures. None of the effects of the combined drug and alcohol conditions differed significantly from the effects of alcohol alone. 相似文献
86.
Background: The results from our 1 year placebo-controlled maintenance/discontinuation study in remitted panic disorder with agoraphobia patients confirmed the significant prophylactic effectiveness of imipramine maintenance treatment but suggested that this may be necessary in only 37% of the patients who relapse following discontinuation of 6 months acute imipramine treatment. This paper presents pilot data from a second year extension of the above-mentioned study with the aim of exploring the putative protective effects of maintenance imipramine therapy beyond the 1st year. Method: Eighteen patients from the 30 who survived, in stable remission, the first 12 months of the maintenance/discontinuation study gave written consent to participate in a double-blind 2nd year extension phase with the knowledge that those on placebo will continue on the same condition (N = 7, PBO–PBO) and those on imipramine (N = 11) will be rerandomized to 2nd year maintenance (N = 4, IMI–IMI) or placebo substitution (N = 7, IMI–PBO). The procedures continued unchanged from that of the 1st year of the study and patients were followed with planned assessments every 2 months over the second 12-month experimental period of the study. Results: None of the IMI–IMI patients relapsed, two (28.5%) of the IMI–PBO patients relapsed, and two (28.5%) of PBO–PBO patients relapsed. The mean estimated time without relapse was 10 months and 9 months for IMI–PBO and PBO–PBO, respectively. The estimated probability of not relapsing was .64 for IMI–PBO and .60 for PBO–PBO (Mantel-cox test
1
2
= .84, p = .77). Conclusion: These interlocking controlled observations tentatively suggest that a substantial degree of prophylactic efficacy continues and that a substantial need for continued prophylaxis exists beyond the 1st year of maintenance imipramine treatment in panic disorder with agoraphobia patients. 相似文献
87.
目的:评价安非他酮治疗抑郁症的疗效和安全性。方法将60例符合CCMD-3诊断标准的抑郁症患者随机分为安非他酮组和丙米嗪组各30例,分别治疗6周。采用汉密尔顿抑郁量表( HAMD)评定疗效,采用副反应量表( TESS)评定药物的不良反应。结果两组治疗后HAMD评分均较治疗前有显著降低( P﹤0.05),治疗1、2、4、6周末两组间HAMD评分均无显著差异( P﹥0.05)。治疗第4、6周末,安非他酮组TESS评分低于丙米嗪组,差异有显著性(P﹤0.05)。结论安非他酮治疗抑郁症有效,且不良反应发生率低于丙米嗪。 相似文献
88.
Arrabi Easwaranathan Beril Inci Sam Ulrich Lars Brunken Violetta Nikiforova Ulf Norinder Stephen Swanson Vesna Munic Kos 《Journal of pharmaceutical sciences》2019,108(1):652-660
Many marketed pharmaceuticals reach extremely high tissue concentrations due to accumulation in lysosomes (lysosomotropism). Quantitative prediction of intracellular concentrations of accumulating drugs is challenging, especially for macrocyclic compounds that mainly do not fit in current in silico models. We tested a unique library of 47 compounds (containing 39 macrocycles) specifically designed to cover the entire range of accumulation intensities observed with pharmaceuticals so far. For the first time, we show that intracellular concentration of compounds measured by liquid chromatography with tandem mass spectrometry correlates with the induction of phospholipidosis and inhibition of autophagy, but the highest correlation was observed with the increase of lysosomal volume (R = 0.95), all measured by high-throughput imaging assays. Based only on imaging data, we developed a 5-class in vitro model for the prediction of compound accumulation with the accuracy of 81%. The measured change of total lysosomal volume can thus be used in high-throughput screening for determination of the actual intensity of intracellular accumulation of new macrocyclic compounds. The models are largely based on macrocycles, greatly improving the screening and prediction of intracellular accumulation of this challenging class. However, all tested nonmacrocyclic compounds fitted well in the models, indicating potential use of the models in broader chemical space. 相似文献
89.
90.
Summary Seventeen hospitalized patients (age 39–66 years), received a loading dose of 100 mg imipramine HCl and then 50 mg b.i.d. The 12-h plasma concentration at steady-state varied between 40–637 nmol/l for imipramine, 49–1148 nmol/l for desipramine and 89–1603 nmol/l for imipramine + desipramine. Guided by plasma level monitoring, a final therapeutic plasma level between 548–910 nmol/l for imipramine + desipramine was achieved (therapeutic dose range: 50–400 mg/day). Mean time to reach the therapeutic level was 19 days. The mean 2-OH-imipramine/imipramine ratio was 0.24 and mean 2-OH-desipramine/desipramine ratio was 0.56. There was a significant intrapatient correlation between the two ratios, both during 100 mg imipramine/d and at the therapeutic dose level. A low ratio was associated with high imipramine and particularly with a high desipramine level. Well defined steady state levels were established at two different dose levels in 12 patients and at three dose levels in 5 patients. With increasing dose there was a marked and disproportionate rise in the desipramine level and to some extent in the imipramine level. Saturation of imipramine and desipramine hydroxylation appeared to be responsible for the dose-dependent kinetics. Concomitant treatment with levomepromazine and perphenazine in one patient resulted in a significant rise both in imipramine and desipramine concentration, apparently due to inhibition of the hydroxylation. Eleven out of twelve endogenously depressed patients responded completely to treatment, whereas the response was poor in the non-endogenously depressed patients despite optimal drug levels. 相似文献