舍曲林与氯米帕明治疗强迫症对照观察

目的：探讨舍曲林与氯米帕明治疗强迫症的临床疗效和安全性。方法将62例强迫症患者随机分为两组,分别给予舍曲林、氯米帕明治疗,观察8周。采用耶鲁‐布朗强迫量表、副反应量表评定临床疗效及不良反应。结果治疗2周末起两组耶鲁‐布朗强迫量表评分均较治疗前显著降低（P＜0．01）,同期两组比较差异无显著性（P＞0．05）。两组总有效率比较差异无显著性（P＞0．05）,舍曲林组不良反应发生率显著低于氯米帕明组（P＜0．01）。结论舍曲林治疗强迫症疗效显著,与氯米帕明相当,但舍曲林安全性高。     

盐酸氯米帕明注射液含量的酸性染料比色法测定

本文用酸性染料比色法测定盐酸氯米帕明注射液的含量，能消除附加剂的干扰，测定波长４１７ｎｍ，回收率９９．９９％，ＲＳＤ０．４８％。操作简便、快速，结果稳定。     

Fluvoxamine in obsessive-compulsive disorder: similar efficacy but superior tolerability in comparison with clomipramine

Some meta-analyses have suggested that the selective serotonin reuptake inhibitors (SSRIs) are less effective than clomipramine in the treatment of obsessive-compulsive disorder (OCD). The aim of this double-blind, randomised, multicentre study was to directly compare the efficacy and safety of fluvoxamine and clomipramine in patients with OCD. A total of 227 patients were randomised to flexible doses of fluvoxamine or clomipramine (both 150-300 mg/day) for 10 weeks. Fluvoxamine and clomipramine were both clinically effective and there were no statistically significant differences between the two treatment groups, at any visit, on the National Institute of Mental Health Obsessive-Compulsive global rating scale, the Yale-Brown Obsessive-Compulsive scale (total score and obsession and compulsion subscores), the Clinical Global Impression severity of illness and global improvement subscales, the Clinical Anxiety Scale and the 17-item Hamilton Depression Rating Scale. However, there were differences in safety between the two treatments. Compared with fluvoxamine-treated patients, those treated with clomipramine had more anticholinergic side effects (dry mouth, constipation and tremor) and premature withdrawals due to adverse events (18 versus 9). The results from this controlled study indicate that fluvoxamine is as effective as clomipramine in the treatment of OCD but has a better tolerability profile. Copyright 2001 John Wiley & Sons, Ltd.     

Chronic administration of clomipramine prevents the increase in serotonin and noradrenaline induced by chronic stress

The effects of chronic clomipramine administration (15 mg/kg daily for 23 days) on changes in serotonin (5-hydroxytryptamine, 5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline (NA) induced by chronic stress have been studied in the rat brain. Chronic stress increased 5-HT in midbrain, pons and hippocampus, 5-HIAA in frontal cortex, midbrain, pons and hippocampus, and NA in midbrain and striatum. Chronic clomipramine significantly decreased the levels of 5-HT in most regions. In hypothalamus, hippocampus and perhaps in frontal cortex this effect possibly reflects decreased synthesis caused by an action on presynaptic 5-HT receptors. However, in midbrain, pons and striatum decreased 5-HT could not be attributed to a decrease in its synthesis since 5-HIAA also increased. This drug treatment also reduced NA in all regions except the striatum. Nevertheless, conclusions on NA synthesis or turnover cannot be drawn since only NA levels were measured. When administered concurrently, chronic clomipramine prevented the increases in 5-HT, 5-HIAA and NA produced by chronic stress. These results are in good accordance with previous findings showing that chronic antidepressant treatment also prevented behavioural disturbances induced by chronic stress.     

Serum cortisol concentration in patients with major depression after treatment with clomipramine

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and elevated cortisol (CORT) levels are characteristics of the pathophysiology of major depressive disorder.The aim of this study was to determine whether increased plasma CORT levels appear in patients with major depression and if effective antidepressant treatment by clomipramine (CLO) leads to regulation of CORT level. Plasma CORT levels were measured using high performance liquid chromatography (HPLC) methods in patients with major depression at time zero (before therapy) and after 3 h, 24 h, 4, 6 and 8 weeks of CLO administration. The study included 17 patients (12 women, 5 men; mean age 54.5 years, SD = 12.3) and 21 healthy comparison subjects. The patients had a mean score on the 21-item Hamilton Depression Rating Scale (HDRS) of 26.8 (range 22–35). Eight of the patients with major depression recruited for the study showed a 46% increase in CORT concentration compared to the established standard. In 13 patients treated with CLO, serum CLO levels reached a therapeutic range. In recovered depressed patients, antidepressant treatment significantly reduced HDRS scores from the 6th week of treatment. Adrop in plasma CORT levels in recovered depressed subjects occurred 0 to 6 weeks after CLO treatment (n = 5, p < 0.046). However, neither subject group exhibited any definitive markers of CORT secretion. In the population studied, patients had distinct profiles of HPA axis dysregulation. Finding a linear correlation between lower CORT secretion and therapeutic plasma CLO levels is the first aim of monitored therapy and may be important for understanding the pathophysiology of major depressive disorder.     

Sympathomimetic effects of amezinium on the cardiovascular system and plasma catecholamines in man

Summary Thirty one in-patients suffering from depression were treated orally with clomipramine (Cl) at various dosage, for 28 days, after a “wash-out” period of three days. In 17 patients receiving 75 mg per day of Cl, steady state plasma levels of Cl were reached at Day 14, and steady state plasma levels of its active metabolite, desmethylclomipramine (DMCl), were reached at Day 21. In contrast, in 7 other patients receiving a dosage increasing to 150 mg per day at Day 7, mean plasma levels of Cl and DMCl continued to rise during the entire treatment period. At the steady state, a correlation was found between Cl dosage expressed as mg kg body weight and the plasma concentration of Cl and DMCl. Factors such as tobacco and alcohol consumption seem to modify the Cl/DMCl ratio. A comparison of clinical response with plasma levels of Cl, DMCl and Cl + DMCl showed a significant negative linear correlation.     

氯米帕明、帕罗西汀致咳嗽

1名72岁抑郁症女性患者在13年的时间内,先后服用了氯米帕明(最高剂量75mg/d)和帕罗西汀(最高剂量70mg/d)。患者在应用该2药后均出现咳嗽,咽痒,停用后咳嗽消失,再次服药咳嗽再现。     

Pharmacokinetics of clomipramine, an antidepressant, in poloxamer 407-induced hyperlipidaemic model rats

Objective This study was undertaken to investigate the effects of hyperlipidaemia on the pharmacokinetics of clomipramine, an antidepressant, particularly addressing the change of clomipramine distribution to plasma components in poloxamer 407‐induced hyperlipidaemia model rats. Methods Clomipramine pharmacokinetic studies in hyperlipidaemic rats were performed with clomipramine continuous infusion. Furthermore, clomipramine protein binding and distribution to the brain and plasma components such as lipoproteins were investigated. Key findings Mean plasma concentration of clomipramine at steady state during continuous infusion (17.5 µg/min/kg) in hyperlipidaemic rats (0.45 ± 0.01 µg/ml) was significantly higher than that in the control rats (0.30 ± 0.02 µg/ml). However, the amount of clomipramine in the brain in hyperlipidaemic rats (0.31 ± 0.06 µg/g) was dramatically lower than in the control rats (1.89 ± 0.13 µg/g). However, the plasma unbound fraction in hyperlipidaemic rats (0.98 ± 0.05%) was significantly lower than that of the control rats (6.51 ± 0.62%). Conclusions Lower distribution to the brain and lower plasma clearance of clomipramine in hyperlipidaemic rats resulted from lower plasma unbound fraction because of higher lipid‐rich protein contents in blood. Results of this study provide useful information for dosage adjustment of clomipramine in hyperlipidaemia.     

Correlation of Plasma and Peritoneal Diasylate Clomipramine Concentration with Hemodynamic Recovery after Intralipid Infusion in Rabbits

Objectives:  Drug sequestration to an expanded plasma lipid phase has been proposed as a potential mechanism of action for lipid emulsions in lipophilic cardiotoxin overdose. The authors set out to document plasma and peritoneal diasylate clomipramine concentration after resuscitation with lipid emulsion in a rabbit model of clomipramine-induced hypotension.
Methods:  Twenty sedated mechanically ventilated New Zealand White rabbits were allocated to receive either 12 mL/kg 20% Intralipid or 12 mL/kg saline solution, following clomipramine infusion to 50% baseline mean arterial pressure (MAP). Hemodynamic parameters and serum clomipramine concentration were determined to 59 minutes. Peritoneal dialysis with 20% Intralipid or saline solution was evaluated for clomipramine concentration.
Results:  Mean arterial pressure was greater in lipid-treated animals as assessed by repeated-measures analysis of variance (F[1,14] = 6.84; p = 0.020). Lipid infusion was associated with elevated plasma clomipramine concentration and reduced initial volume of distribution (Vd; 5.7 [±1.6] L/kg lipid vs. 15.9 [±7.2] L/kg saline; p = 0.0001). Peritoneal diasylate clomipramine concentration was greater in lipid-treated animals (366.2 [±186.2] μg/L lipid vs. 37.7 [±13.8] μg/L saline; p = 0.002).
Conclusions:  Amelioration of clomipramine-induced hypotension with lipid infusion is associated with reduced initial Vd and elevated plasma clomipramine concentration consistent with intravascular drug–lipid sequestration. Concomitant peritoneal dialysis with lipid emulsion enhances clomipramine extraction.     

氯丙米嗪对大鼠局灶性脑缺血损伤后运动功能的作用

目的：研究氯丙米嗪对脑缺血的作用。方法：在局灶性脑缺血的大鼠应用氯丙嗪，与脑缺血对照组比较，在缺血后1，3，7，14和28d测试神经学功能。结果：氯丙米嗪组的网屏握持功能较对照组明显改善，而两组的胶布撕脱试验之间无明显差别。结论：氯丙米嗪可提高局灶性脑缺血后的肌力。