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71.
To further test the new hypersensitive postsynaptic serotonin (5-HT) receptor theory of depression based on our animal model, it was necessary to demonstrate that some of the currently used antidepressive drugs can block D,L-5-hydroxytryptophan (5-HTP) induced depression acting through postsynaptic rather than presynaptic mechanisms. Rats working for milk reinforcement and exhibiting behavioral depression following administration of 5-HTP (IP) were pretreated (1 hour before the 5-HTP injection) with fluoxetine (5 mg/kg IP) or methysergide (5 mg/kg IP) to establish a behavioral basis for distinguishing between pre- and postsynaptic events, respectively. Fluoxetine, a known specific uptake blocker of 5-HT, potentiated the depressive effect of 12.5 mg/kg 5-HTP by 200%. Methysergide, a postsynaptic blocker of 5-HT, almost completely (93%) abolished the depressive effect of 50 mg/kg 5-HTP. Since acute pretreatment with comparable clinical doses of the antidepressive drugs, mianserin, amitriptyline, imipramine, or iprindole, resulted in blockade of the 5-HTP induced depression by 70, 50, 40, and 20% respectively, these drugs can act as antagonists of 5-HT at the postsynaptic serotonin receptor. When these results are viewed in terms of recent data reported from CNS binding studies, the therapeutic effects of some antidepressants may be explained by their postsynaptic rather than presynaptic effects at central serotonergic receptors. 相似文献
72.
73.
背景 阿米替林(amitriptyline,AMI)是三环类抗抑郁药(tricyclic antidepressants,TCAs)在神经病理性疼痛(neuropathic pain,NPP)中应用最广泛的药物,历年文献分析总结证实TCAs对NPP有效,其中证据最确切的是AMI,并且其镇痛作用独立于抗抑郁作用,尤其适用... 相似文献
74.
The aim of the study was to evaluate the influence of quinidine, a P-glycoprotein inhibitor, on oral bioavailability and on intestinal secretion of amitriptyline, a tricyclic antidepressant. Amitriptyline was administrated intravenously (5 mg/kg) and orally (50 mg/kg) to rabbits, with and without quinidine. Jejunal segments of rats were mounted on diffusions chambers and the permeation of amitriptyline was measured across the tissue in luminal–serosal (LS) and serosal–luminal (SL) directions, with and without quinidine. Finally, an in situ recirculating intestinal perfusion model was performed in rabbits to study amitriptyline permeation in LS direction with and without quinidine. Absolute oral bioavailability (F) of amitriptyline was significantly increased more than three-fold in presence of quinidine (F = 0.6 ± 0.4% versus 1.9 ± 1.1%). The apparent permeability coefficients in SL direction were significantly higher than in LS direction (Papp (SL) = 6.01 ± 2.42 versus Papp (LS) = 4.90 ± 2.73 × 10−4 cm min−1). In presence of quinidine, the intestinal absorption was increased (Papp (LS) = 4.02 ± 2.91 versus Papp (LS) = 5.99 ± 2.43 × 10−4 cm min−1) and the intestinal secretion was decreased (Papp (SL) = 4.58 ± 0.54 versus Papp (LS) = 3.63 ± 1.46 × 10−4 cm min−1) but not significantly. In conclusion, P-glycoprotein appears to be involved in oral amitriptyline absorption but other intestinal uptake and efflux transporters maybe implicated. 相似文献
75.
《Current medical research and opinion》2013,29(8):602-606
SummaryA study was carried out in 6 healthy volunteers to test the hypothesis that weight gain associated with amitriptyline treatment may be due to hypoglycaemia caused by increased circulating blood insulin. Subjects were treated with 50 mg amitriptyline b.d. for 28 days. Estimations made of serum levels of amitriptyline and its metabolite nortriptyline showed a steady state by the 10th day. No significant weight-gain was observed in any of the volunteers, although 2 reported an increase in appetite. There were no significant differences in any of the glucose tolerance curves, fasting or peak insulin levels or in the glucose I insulin curves for Days 0, 14 and 28. 相似文献
76.
Migraine is increasingly recognized as a channelopathy, and abnormalities of voltage-activated ionic channels could represent the molecular basis for the altered neuronal functioning. The high-voltage-activated (HVA) Ca2+ channels in the trigeminovascular system play a role in the pathophysiology of migraine. In the present study, effects of amitriptyline (AMT), a commonly used migraine prophylactic drug, on the HVA calcium currents (ICa) were examined in mouse trigeminal ganglion neurons using whole-cell patch clamp technique. AMT produced concentration- and use-dependent inhibition of HVA ICa. Bath application of GÖ-6983 (a selective protein kinase C inhibitor) or H89 (a protein kinase A inhibitor) did not reduce the AMT-induced inhibition of HVA ICa. A similar inhibition was observed when calcium imaging was used to directly monitor the effects of AMT on KCl-induced increments of intracellular Ca2+ concentration ([Ca2+]i). By blocking HVA Ca2+ channels and Ca2+ entry into cells, AMT could prevent the release of neurotransmitters and help restore the neuronal threshold for excitation. Our findings suggest interesting therapeutic mechanisms for AMT in migraine prevention. 相似文献
77.
多潘立酮联合阿米替林治疗功能性消化不良的meta分析 总被引:1,自引:0,他引:1
目的对多潘立酮联合阿米替林治疗功能性消化不良的疗效及安全性进行评价。方法计算机检索1991年01月01日至2014年06月01日中国学术期刊全文数据库(CNKI)、维普中文科技期刊数据库(VIP)、万方数据库(WANFANGDATA)、中国生物医学文献数据库(CBMdisc)、Pubmed数据库、Google Book Search等有关多潘立酮联合阿米替林治疗功能性消化不良的随机对照试验(RCT)文献,补充手工检索文献。应用Rev Man5.2软件对入选试验进行Meta分析。结果共8项随机对照试验符合入选标准,共743例功能性消化不良患者,其中接受多潘立酮联合阿米替林治疗共372例患者(试验组),371例患者单用多潘立酮治疗(对照组)。Meta分析结果显示试验组总体有效率(92.5%)明显高于对照组(74.9%,RR:1.23,95%CI:1.16~1.32,P0.000 01),上腹痛腹胀、恶心呕吐、烧心反酸等症状显效率(64.8%)也明显高于对照组(42.0%,RR:1.54,95%CI:1.34~1.77,P0.000 01)。两组不良反应发生率无统计学差异(RR:1.40,95%CI:0.71~2.78,P=0.33)。结论多潘立酮联合阿米替林治疗功能性消化不良疗效优于单用多潘立酮,安全性好,可以成为临床治疗功能性消化不良的一种较佳治疗方案。 相似文献
78.
Perry N. Fuchs William R. Lariviere Melissa Balinsky Ronald Melzack 《Pathophysiology》1996,3(4):227-231
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. 相似文献
79.
帕罗西汀治疗脑卒中后抑郁障碍的对照研究 总被引:1,自引:0,他引:1
袁文林 《中国实用神经疾病杂志》2004,7(3):8-9
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。 相似文献
80.
西酞普兰治疗抑郁症的疗效对照研究 总被引:2,自引:0,他引:2
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. 相似文献