Acute amitriptyline treatment produces non-opioid-mediated analgesia in the formalin and bee venom tests

Tricyclic antidepressants are often effective for the management of persistent pain, and several neurochemical mechanisms have been proposed. The purpose of the present study was to examine the effect of amitriptyline (AMI) in two animal models of inflammatory pain, the formalin test and the bee venom test, and to ascertain the effect of naloxone on amitriptyline analgesia. A single dose of AMI (20 mg/kg) was found to significantly decrease both phases of formalin pain responses and the initial 10 min of bee venom pain responses. However, naloxone (3 mg/kg) had no effect on AMI analgesia in either test. The results show that single doses of AMI can decrease pain behavior in tests of tonic pain and suggest that non-opioid mechanisms may play a role in addition to opioid mechanisms demonstrated in earlier studies.     

阿米替林、美舒郁对血流动力学影响的脉图检测研究

目的　观察研究阿米替林、美舒郁造成的血流动力学改变 ,对比 2药对心血管功能的不同影响。方法　把符合条件的 2 0 8例抑郁症患者 ,随机分成两组 ,一组用阿米替林治疗 ,一组用美舒郁治疗 ,并在用药前及用药后 1周末、2周末、4周末用血液循环动力学脉图检测仪检测病人的血流动力学参数 ,观察项目 :HR、ECV、MEC、LME、MIT、MVO。结果　阿米替林组 1周末即有 MIT改变。自 2周末各个参数均出现明显差异 (P<0 .0 5 ) ,到 4周末 ECV、LME、MVO的改变尤为明显(P<0 .0 0 1 )。而美舒郁组只有 LME 4周末有明显降低 (P<0 .0 5 )。结论　美舒郁抗抑郁治疗时对心脏的影响较小 ,而阿米替林对心脏有明显的影响 ,表现为心率加快 ,有效循环血容量降低 ,心肌耗氧量明显增加 ,心肌供血障碍 ,左室效能降低 ,同时 ,用药时间越长 ,剂量越大 ,对心脏的影响越明显     

Amitriptyline pharmacokinetics in experimental spinal cord injury in the rabbit

Previous studies have demonstrated that pharmacokinetic behavior of several drugs such as paracetamol, theophylline, and aminoglycosides are significantly altered in spinal cord injured patients. No pharmacokinetic study of amitriptyline has been performed in patients and experimental models of spinal cord injury. Pharmacokinetic parameters of amitriptyline in orally treated rabbits subjected to laminectomy and spinal cord injury compared with those underwent laminectomy alone. Among twenty four male rabbits were included in this study, nine of them subjected to spinal cord injury at the 8(th) thoracic level by knife severance method and six rabbits underwent laminectomy alone (sham group) and nine rabbits treated as control. All received a single oral dose of amitriptyline (20 mg/kg) 24 h after injury. Blood sampling were done at predetermined times to 36 h after drug administration. Amitriptyline concentration in serum samples was determined by high-performance liquid chromatography. Pharmacokinetic parameters including maximum concentration (C(max)), time to reach maximum concentration (T(max)), half life, and the area under the curve to last detectable concentration time point (AUC(0-t)) were directly determined from the concentration-time curve. Maximum concentration was observed at 6.5 h after administration in sham group with a concentration of 439.6 ng/ml, whereas in SCI group T(max) was at 2.7 h with a concentration of 2763.9 ng/ml. In control group it was 3.3 h and 396 ng/ml, respectively. In SCI group, AUC was 9465.6 ng.h/ml and half life was 6 h and for control group it was 2817.4 ng.h/ml and 6.4 h, respectively. Statistical analysis of data showed that SCI didn't induce significant changes in amitriptyline pharmacokinetic parameters.     

帕罗西汀治疗抑郁症临床对照研究

目的：观察帕罗西汀治疗抑郁症的疗效。方法：采用开放性对照研究方法,用帕罗西汀与阿米替林治疗抑郁症各３０例,共６周,诊断依据ＣＣＭＤ－２－Ｒ标准分为帕罗西汀组和阿米替林组,采用ＨＡＭＤ,ＣＧＩ－ＳＩ及ＴＥＳＳ评定。结果：帕罗西汀治疗抑郁症显效率７０．０％,阿米替林７６．７％,两组疗效相似（Ｐ〉０．０５）。前者副作用较的者少而程度轻微易于耐受。结论：帕罗西汀是有效的抗抑郁药,不良反应轻微。     

帕罗西汀治疗脑卒中后抑郁障碍的对照研究

目的比较帕罗西汀和阿米替林对脑卒中后抑郁障碍的疗效及神经功能康复的影响。方法 应用帕罗西汀和阿米替林进行对照治疗研究,采用汉密尔顿抑郁量表(HAMD)和爱丁堡-斯堪的纳维亚卒中量表(MESSS)评定疗效。结果 帕罗西汀和阿米替林对脑卒中后抑郁障碍的疗效相当,但帕罗西汀起效较快,且不良反应较少而轻微。结论 帕罗西汀可明显改善脑卒中后抑郁障碍的程度,并能促进神经功能康复。     

阿米替林对非酒精性脂肪性肝病细胞模型脂质沉积及生化代谢的影响

目的探讨阿米替林通过调节酸性鞘磷脂酶(ASM)/神经酰胺(CE)通路对非酒精性脂肪性肝病(NAFLD)细胞模型脂质及生化代谢的影响。方法体外培养HepG2和L02细胞构建NAFLD细胞模型,MTT比色法测定细胞增殖率,油红O染色观察细胞内脂滴变化。实验分组:正常对照组、模型组、Ami组、TNFα组、Ami+TNFα组。全自动生化分析仪检测细胞内TG、TC及细胞上清液ALT、AST水平,ELISA法检测细胞内总的CE、ASM水平,Western Blot检测细胞内ASM蛋白的表达;实时荧光定量PCR检测细胞内ASM mRNA水平的表达。计量资料多组间比较采用单因素方差分析,进一步两两比较采用Turkey检验。结果与正常对照组相比,NAFLD模型组ASM蛋白和mRNA表达量以及CE、TG、TC、ALT、AST水平明显升高(P值均<0.05);与模型组相比,Ami组ASM蛋白和mRNA表达量以及CE、TG、TC、ALT、AST水平明显降低(P值均<0.05),TNFα组ASM蛋白和mRNA表达量以及CE、TG、ALT、AST水平明显升高(P值均<0.05);与TNFα组比较,Ami+TNFα组ASM蛋白和mRNA表达量以及CE、TG、TC、ALT、AST水平明显降低(P值均<0.05)。结论ASM/CE通路促进脂质积聚、导致脂肪变,阿米替林可通过抑制该通路改善NAFLD肝细胞的脂质沉积。     

西酞普兰治疗抑郁症的疗效对照研究

目的 探讨选择性五羟色胺再摄取抑制剂西酞普兰治疗抑郁症的疗效及安全性.方法 将60例符合CCMD-3诊断标准的抑郁症病人随机分为两组,分别给予西酞普兰和阿米替林治疗.疗程6周.采用汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）评定疗效,并以不良反应量表（TESS）评定不良反应.结果 西酞普兰组显效率为83.33%,阿米替林组为76.67%,差异无显著性.西酞普兰不良反应少而轻微,主要有恶心、口干、头痛.结论 西酞普兰是一见效快、疗效肯定及不良反应少而轻微的抗抑郁药.     

Prolonged Toxicity after Amitriptyline Overdose in a Patient Deficient in CYP2D6 Activity

Introduction

Amitriptyline and its metabolite, nortriptyline, are metabolized, in part, by CYP2D6, a polymorphic enzyme. About 8% of Caucasians are deficient in CYP2D6 activity.

Case Report

We present the case of a comatose woman who intentionally overdosed on amitriptyline and displayed rising serum total tricyclic antidepressant concentrations for at least 6 days after admission. Serial immunoassay total tricyclic antidepressant concentrations in our patient showed gradual decline beginning day 7, although the patient did not regain normal mental status until day 12. Genotyping revealed the patient to be homozygous for the CYP2D6*4 allele, the most common explanation of CYP2D6 enzymatic deficiency among Caucasians. Patients taking tricyclic antidepressants who are homozygous for CYP2D6*4 demonstrate >3 times concentration–time curve (AUCs) and prolonged elimination half-lives, especially of secondary amines such as nortriptyline.

Discussion

We believe this is the first report describing toxicokinetics after tricyclic antidepressant overdose in a CYP2D6-deficient patient.     

三联法治疗大学生肠易激惹综合征临床疗效观察

目的：探讨丽珠肠乐胶囊、得舒特联合抗抑郁药物阿米替林三联法治疗大学生肠易激惹综合征的临床疗效。方法：将41例肠易激惹大学生患者随机分为两组,治疗组21例,用丽珠肠乐胶囊、得舒特联合抗抑郁药物阿米替林三联法治疗;对照组20例,单纯采用丽珠肠乐胶囊及得舒特治疗,4周后进行疗效评价。结果：治疗组显效14例,有效6例,无效1例,总有效率为95%,疗效优于对照组总有效率（65%）（P〈0.05）。结论：采用丽珠肠乐胶囊、得舒特联合抗抑郁药物阿米替林三联法治疗大学生肠易激惹综合征的疗效确切,值得临床推广应用。     

曲唑酮与阿米替林治疗抑郁症的双盲对照试验

目的　评估曲唑酮治疗抑郁症的效果。方法　应用曲唑酮 (男性 1 3例 ,女性 6例 ;年龄 3 6.2± 1 3 .7岁 )与阿米替林(男性 1 1例 ,女性 8例 ,年龄 3 4 .6± 1 2 .5岁 )治疗抑郁症 3 8例 ,并进行随机双盲对照。初始剂量均为 50 mg/日 ,PO,1 0日内渐增至 1 50～ 3 0 0 mg/日 ,观察 6周。采用 HAMD、HAMA及 TESS量表评定。结果　曲唑酮与阿米替林疗效相仿。HAMD总分及其因子分 ,HAMA评分疗后均比疗前显著降低 ,但 2组间比较 ,差别均无显著意义 (P>0 .0 5)。曲唑酮的主要不良反应为镇静 ,其对植物神经及心血管方面的影响明显较阿米替林为轻。结论　曲唑酮是一种安全有效的抗抑郁药