西酞普兰与马普替林治疗老年抑郁症的对照研究

目的探讨西酞普兰与马普替林治疗老年抑郁症的疗效和不良反应。方法将80例老年抑郁症患者随机分成两组，一组服用西酞普兰，另一组服用马普替林，疗程6周。采用汉密顿抑郁量表（HAMD）及药物副反应量表（TESS）定疗效和不良反应。结果西酞普兰组显效率为80％；马普替林组显效率为72．5％，两组差异无显著性。西酞普兰组不良反应较马普替林组少而轻。结论西酞普兰治疗老年抑郁症的疗效确切，起效快，不良反应轻，依从性好。     

米氮平与马普替林治疗抑郁症对照研究

目的 评价米氮平与马普替林治疗抑郁症的疗效和不良反应.方法 将符合CCMD-3诊断标准的60例抑郁症住院和门诊患者,随机平分为两组,分别给予米氮平和马普替林治疗,疗程6周.用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)和副反应量表(TESS)评定疗效和不良反应.结果 米氮平与马普替林治疗抑郁症的疗效接近,但前者起效更快,不良反应少于后者.结论 米氮平是一种安全、有效的新一代抗抑郁药,可以作为治疗抑郁症的第一线抗抑郁药使用.     

Effect of the antidepressant maprotiline on calcium movement and the viability of renal tubular cells

In Madin-Darby canine kidney (MDCK) cells, the effect of maprotiline, an antidepressant, on intracellular Ca²⁺ concentration ([Ca²⁺]_i) was measured using fura-2. Maprotiline (>2.5 µM) caused a rapid rise of [Ca²⁺]_i in a concentration-dependent manner (EC₅₀ 200 µM). Maprotiline-induced [Ca²⁺]_i rise was reduced by removal of extracellular Ca²⁺ or by addition of La³⁺, but was not altered by voltage-gated Ca²⁺-channel blockers. Maprotiline-induced Mn²⁺ influx-associated fura-2 fluorescence quench directly suggests that maprotiline caused Ca²⁺ influx. In Ca²⁺-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca²⁺-ATPase, caused a monophasic [Ca²⁺]_i rise, after which the increasing effect of maprotiline on [Ca²⁺]_i was nearly abolished; also, pretreatment with maprotiline reduced a portion of thapsigargin-induced [Ca²⁺]_i rise. U73122, an inhibitor of phospholipase C, abolished [Ca²⁺]_i rise induced by ATP (but not by maprotiline). Overnight incubation with 1–10 µM maprotiline enhanced cell viability, but 20–50 µM maprotiline decreased it. These findings suggest that maprotiline rapidly increases [Ca²⁺]_i in renal tubular cells by stimulating both extracellular Ca²⁺ influx and intracellular Ca²⁺ release, and may modulate cell proliferation in a concentration-dependent manner.     

米氮平与马普替林治疗难治性抑郁症对照观察

目的:评价米氮平与马普替林治疗难治性抑郁症的疗效和不良反应。方法:采用随机对照方法,分别给予米氮平和马普替林治疗,疗程6周。应用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、临床疗效总评量表(CGI-SI)、和副反应量表(TESS)于疗前、疗后1,2,4,6,Weeks进行疗效和不良反应评定。结果:米氮平组治疗6周末HAMg)平均分值从31.5降至17.2分,HAMA平均分值从24.7降至14.4分。马普替林组分别从32.2降至22.7分和26.9降至21.5分。两组有效者分别为12例和4例。米氮平较马普替林见效快,副作用发生率低而轻微。结论:米氮平疗效优于马普替林,可用于治疗难治性抑郁症。     

Frequency-dependent effects of amitriptyline and maprotiline on conduction in the guinea pig His-Purkinje-system in vivo

In the Cardiac Arrhythmia Suppression Trial antiarrhythmic drug therapy with slow kinetic sodium channel blockers (class Ic antiarrhythmic drugs) was associated with excess mortality, presumably due to drug induced proarrhythmia. It has been suggested that the degree of rate-dependent conduction slowing produced by agents that have sodium channel blocking properties may be related to the proarrhythmic propensity of these agents.In the present study, rate-dependent conduction slowing by the antidepressants amitriptyline and maprotiline was investigated in anesthetized guinea pigs. After electrical ablation of the sinus node the left atrium was stimulated at cycle lengths between 200 ms and 500 ms. His bundle electrograms were registered by means of an epicardial electrode. Drugs were administered by i.v. infusion of 0.2 mg kg^–1 min^–1 for 30 min followed by 0.1 mg kg^–1 min^–1 for up to 30 min. Both drugs produced substantial rate-dependent conduction slowing within the His-Purkinje-system. The relationship between pacing rate and conduction slowing was well fitted by linear regression. The steepness of the regression line was significantly greater for amitriptyline than for maprotiline (slope factors: 9.10×10^–4±7.85 × 10^–5, n = 6, vs. 6.29×10^–4±2.97×10^–5, n=6, P<0.001), indicating that conduction slowing by amitriptyline exhibits a greater degree of rate-dependence than conduction slowing by maprotiline. On abruptly changing the driving cycle length from 500 ms to 300 ms, conduction slowing reached a new steady state with rate constants of 0.83±0.093 beat^–1 (amitriptyline) and 0.14±0.05 beat^–1 (maprotiline, P<0.001). Following interruption of rapid pacing at a cycle length of 250 ms, conduction slowing recovered with time constants of 332.4±52.8 ms (amitriptyline) and 1088.1 ± 143.5 ms (maprotiline, P = 0.001). Thus, amitriptyline exhibited fast kinetic properties similar to class Ib antiarrhythmic action while the slower kinetic properties of maprotiline resembled those of class Ia agents.Deceased Correspondence to: H. Todt at the above address     

麦普替林治疗注意缺陷多动障碍的疗效研究

目的　探讨麦普替林治疗注意缺陷多动障碍 (ADHD)的疗效及安全性。方法　符合CCMD 3诊断标准的ADHD患儿 32例 ,单一用麦普替林 2 5～ 12 5mg/d治疗 ,6周后进行临床疗效评定 ,治疗前后采用Conners儿童行为问卷 4 8项家长用症状问卷 (PSQ)评估对照。结果　有效 2 2例 ,有效率 6 8 75 % ,PSQ评估 6项因子分明显下降 ,其中因子Ⅲ (心身问题 )P <0 0 5 ,其余 5项因子分P <0 0 0 1。服药第 1周出现轻度口干、镇静、视物模糊、心跳增快 ,2周后逐步消失。结论　麦普替林治疗ADHD疗效肯定 ,副反应相对较轻 ,可作为治疗ADHD的首选药物之一。     

Non-response to maprotiline caused by ultra-rapid metabolism that is different from CYP2D6?

Case: We are reporting about a patient with major depression who failed to respond to pharmacotherapy due to ultra-rapid metabolism of maprotiline. Under daily oral doses of 175 mg maprotiline, the patient's metabolic ratio (MR) for maprotiline in plasma was 9.2 (expected MR_p: 2.4) and the clearance of maprotiline (CL_M) was 4190 ml · min⁻¹ (expected CL_M = 1220 in extensive metabolisers of CYP2D6). Results: The patient's MR_urine for sparteine was 0.5, which is within the range for extensive metabolisers of CYP2D6. Genotyping did not show a duplication of the CYP2D6L allele. The patient's caffeine half-life was 10 h, thus, precluding ultra-rapid metabolism for CYP1A2. The therapeutic regimen was changed to coadministration of 200 mg maprotiline and 20 mg fluoxetine once per day in order to inhibit metabolism via CYP2D6. Subsequently, MR_p of maprotiline (4.9) and CL_M were reduced (1900 ml · min⁻¹; expected CL_M in poor metabolisers: of CYP2D6 364). This regimen improved the clinical outcome of the underlying disease. Conclusion: We conclude that for the non-response seen with maprotiline, P450 isozymes other than CYP2D6 or CYP1A2 are responsible. As CYP2C19 is involved in the metabolism of a number of tricyclic antidepressants it may be a candidate for ultra-rapid metabolism in this patient. Received: 11 October 1996 / Accepted in revised form: 6 February 1997     

万拉法新与马普替林治疗老年期抑郁症对照研究

目的　比较万拉法新与马普替林治疗老年期抑郁症的疗效和安全性。方法　符合中国精神障碍分类与诊断标准第3版 (CCMD-3 )的 40例老年期抑郁症患者随机分为万拉法新组和马普替林组进行 6周的治疗 ,采用汉密顿抑郁量表(HAMD) ,临床总体评定量表 (CGI)评定临床疗效 ,采用副反应量表 (TESS)评定副反应 ,在治疗前及治疗后 1 ,2 ,4,6周进行评定。结果　万拉法新组显效率为 75 % ,马普替林组显效率为 70 % ,两组之间无显著差异 (χ2 =0 .1 2 5 ,P>0 .0 5 )。万拉法新起效迅速 ,主要副反应为消化道症状、轻度头晕 ;马普替林主要为抗胆碱能和心血管系统副作用。结论　万拉法新治疗老年抑郁症与马普替林与疗效相当 ,起效快 ,副作用较少。     

Plasma tryptophan and tyrosine ratios to competing amino acids in relation to antidepressant response to citalopram and maprotiline

Pretreatment plasma ratios of tryptophan (Trp) and tyrosine (Tyr) to other large neutral amino acids were determined in 27 depressed patients who completed a double-blind trial of citalopram, a selective serotonin uptake inhibitor, against maprotiline, a selective noradrenaline uptake inhibitor.The Trp ratio and the Tyr ratio were decreased in the total patient sample as compared with healthy controls. Plasma Tyr ratio was normal in the endogenous, but significantly decreased in the non-endogenous depressives. There was no significant relationship between the plasma Trp ratio and the probenecid-induced accumulation of 5-HIAA in the CSF, or between the plasma Tyr ratio and HVA level in CSF, whereas the CSF level of MHPG correlated significantly with the plasma Tyr ratio.There was a significantly positive correlation between the Trp ratio, the Tyr ratio, their sum and the final Hamilton depression score in 14 patients treated with citalopram; on the whole, this association was evident also in the endogenous and non-endogenous subgroups. In 13 patients on maprotiline there was a significantly positive correlation between the plasma Tyr ratio and the percent reduction of Hamilton depression score; this association was poor in the endogenous, whereas a trend towards a correlation remained in the non-endogenous subgroup. The results suggest that the plasma Trp and Tyr ratios may be determinants of clinical improvement in depressed patients to treatment with citalopram and maprotiline. However, further studies are needed on larger patient samples to allow a firm conclusion.