Myocardial Pharmacokinetics of Amitriptyline and Clomipramine in the Isolated,Perfused Rabbit Heart

Abstract The myocardial pharmacokinetics of amitriptyline and clomipramine were investigated in isolated rabbit hearts, which were perfused with a modified Krebs-Henseleit solution containing the equimolar concentrations 0.25 or 0.28 μg ml^-1 of the compounds, respectively. The rate of myocardial uptake of the drugs as a function of time was indirectly followed by determinations of the concentrations of the compounds in fractional samples of the coronary output of perfusate. The time course of disposition of amitriptyline from the myocardium was similarly followed after changing from amitriptyline perfusion to perfusion with drug-free liquid. The amitriptyline accumulation and disposition processes were found to fit bi-exponential functions indicating myocardial two-compartment characteristics of the compound. Clomipramine did only exhibit one-compartment myocardial characteristics. The biological half-life of amitriptyline in the myocardium was about 37.7 min. and a pronounced cardiac accumulation of about 340 μg of the compound at steady state was evidenced. The myocardial half-life of clomipramine was about 106 min. and the accumulated amount at steady state was calculated to be 1055 μg. After amitriptyline perfusion an increase in the pharmacokinetic rate constants k₁₀ and k₁₂ and a decrease in the apparent central volume of distribution was observed.     

The influence of ageing on serum levels of tertiary tricyclic antidepressants

The influence of ageing on serum levels of tertiary tricyclic antidepressants (TCAs) was studied in 385 psychiatric inpatients treated daily with one of three TCAs: 157 patients with amitriptyline (154 ± 47 mg, mean dose ± SD), 183 with doxepin (177 ± 59 mg) and 45 with clomipramine (153 ± 51 mg). The patients were divided into three age groups: 125 of them were aged < 35 years, 218 were 35–65 years and 42 were > 65 years. The numbers of blood samples for gas-chromatographic monitoring of steady-state concentrations of serum tertiary and secondary TCAs were 192 for amitriptyline, 240 for doxepin and 138 for clomipramine. The concentrations of serum amitriptyline and nortriptyline rose in an age-related manner. The serum clomipramine and norclomipramine concentrations were higher in the middle-aged than in the young patient groups, whereas serum doxepin and nordoxepin concentrations changed less markedly with advancing age. The variations of serum amitriptyline and nortriptyline concentrations were not greater in old patients than in middle-aged ones. Neither were the variations in doxepin and nordoxepin concentrations enlarged with advancing age (but those in clomipramine and norclomipramine concentrations were wider in middle-aged than in young patients). The number of too high (‘toxic’) TCA concentrations was inconsistently greater in the elderly than in the two younger age groups. The results suggest that the liability of old patients to the adverse effects of TCAs is not—at least with all TCA treatments—due to the enlarged variation in serum drug levels or to the increased frequency of ‘toxic’ serum TCA concentrations.     

米氮平和氯米帕明维持治疗抑郁症对照观察

目的:比较抑郁症患者用米氮平和氯米帕明维持治疗的疗效.方法:将60例门诊抑郁症患者随机分为服用米氮平组和氯米帕明组,均治疗54周,用汉密尔顿抑郁量表(HAMD)临床疗效总评量表(CGI)和副反应量表(TESS)在治疗前及治疗12、54周末比较两组的疗效和依从性.结果:治疗12周两组均有非常显著的疗效,两组间比较差异无显著性;治疗54周以米氮平组显著较好.米氮平组不良反应发生率远低于氯米帕明组.结论:抑郁症患者对米氮平依从性高主要是因疗效好,不良反应轻.     

A Double-Blind Trial of Clomipramine in Premature Ejaculation

Klinische Doppelblindstudie über Clomipramin bei vorzeitiger Ejakulation
Anhand einer klinischen Doppelblindstudie bei 50 Patienten mit Ejakulatio praecox wurde die Wirkung von Clomipramin, einem trizyklischen Antidepressivum, untersucht. Die Patienten wurden in zwei Gruppen aufgeteilt, von denen jede in zwei Versuchsperioden über einen Zeitraum von sechs Wochen kontinuierlich mit dem Medikament beziehungsweise einem Plazebo behandelt wurde. Dadurch konnte die Wirkung von Medikament und Plazebo sowohl zwischen beiden Gruppen als auch innerhalb jeder Gruppe verglichen werden. Bei der Auswertung der Daten ergab sich, daß im Vergleich zur Plazebo-Anwen-dung die Gabe von Clomipramin in einem signifikant höheren Maß zu einem befriedigenden Verkehr führte, ein Effekt, der auch nach Absetzen des Medikaments und Ersatz durch Plazebo anhielt.     

Chronic Treatment with Clomipramine and Desipramine Induces Deficit in Long-Term Visuo-Spatial Memory of Rats

Although the effects of antidepressants in brain neurochemistry have been extensively studied, there are scarce and inconsistent data on the effect of these drugs in learning and memory. The authors studied the effect of daily administration of a single dose of either clomipramine or desipramine, two monoamine-reuptake-inhibitors with preferential serotonergic and noradrenergic profiles, respectively, during 15 days, on the visuo-spatial memory of adults rats measured through their performance in an eight-arm radial maze. Rats receiving 10 mg/kg i.p. daily of clomipramine or desipramine, 30 min before testing, committed a significantly greater number of errors than saline-treated control rats throughout the duration of the test (5 sessions, 15 days), excepting for session one (after 3 days of testing) where there were no differences between the 3 groups of rats. Results indicated that both serotonergic and noradrenergic antidepressants could impair long-term visuo-spatial memory in the rat, whereas inducing no changes in working memory, effects that are likely related to changes in brain monoamine metabolism induced by the antidepressant drugs.     

国产舍曲林与氯丙咪嗪治疗强迫症的对照研究

目的 评价国产舍曲林与氯丙咪嗪治疗强迫症的疗效和安全性.方法 对符合CCMD-3强迫诊断标准,分别接受国产舍曲林和氯丙咪嗪治疗的共50例强迫症患者进行为期8周的观察,并应用Yale-Brown强迫量表(YoBOCS)、Marks恐怖强迫量表(MSCPOR)、HAMD、HAMA和TESS量表评估和比较这2种药物治疗强迫症的疗效和不良反应.结果 经过8周治疗,国产舍曲林组与氟丙咪嗪组疗效相近(P>0.05),国产舍曲林组与氯丙味嗪的显效率(痊愈 显著进步)差异元统计学意义(X2=0.089,P>0.05).国产舍曲林组不良反应发生率明显少于氯丙咪嗪组.结论 国产舍曲林与氟丙味嗪对强迫症均有较好的疗效,但舍曲林具有给药方法简便、不良反应轻等优点.     

强迫症的氯丙米嗪与合并暴露疗法比较研究

目的：探讨暴露疗法对强迫症的疗效,并比较暴露疗法对强迫观念及强迫行为疗效的差异。方法：将符合CCMD－2－R强迫症诊断标准的28例病人,随机将其中的14例在氯丙咪嗪治疗的基础上联用暴露疗法做为研究组,另14例单用氯丙咪溱治疗做为对照组,均系统治疗8周,用耶鲁－布朗强迫症量表（Y－BOCS）减分率评定两组治疗强迫症的疗效。结果：氯丙咪嗪合并暴露疗法组的疗效优于单用氯丙米嗪组,尤其是在控制强迫性行为方面更为突出。结论：氯丙咪嗪合并暴露疗法尤其适用于以强迫行为为主的强迫症病人。     

Tricyclic antidepressant plasma level monitoring: intraindividual variability in everyday practice

Summary The intraindividual variability of tricyclic antidepressant plasma levels (amitriptyline, clomipramine, imipramine and desimipramine) has been examined twice in 127 depressed outpatients. The dosage, route of administration, concomitant drug therapy and clinical condition were identical on the two occasions, which were 1 to 2 months apart.The mean plasma levels of the antidepressant drug and its main metabolite did not differ significantly in the first and second blood samples, indicating little intraindividual variation.