新一代抗抑郁症药物治疗

三环类抗抑郁药（ＴＣＡ）虽疗效确凿，但仍有２０％～３０％无效，而且毒副反应较多。病人对药物的耐受性差，过量易引起中毒甚至死亡。从７０年代起，第一代的抗抑郁药选择性５羟色胺（５ＨＴ）再摄取抑制剂（ＳＳＲＩ）。开始了研制，结构与三环类迥然不同，药理作...     

抗抑郁剂对健康人及以腹泻为主的肠易激综合征患者肠蠕动的影响

抗精神病药物常用来治疗胃肠功能紊乱。治疗后症状改善可归因于情绪的影响,然而这类药物本身也能改变肠蠕动。 1 对象和方法通过对以腹泻为主要症状的肠易激综合征(IBS)患者10例和健康对照组25人的整个肠道通过时间(WGTT)与口——盲肠通过时间(OCTT)的对比,对三环类抗抑郁剂丙咪嗪和选择性5—羟色胺再摄取抑制剂氟苯哌苯醚的疗效进行评估。连续3d早晨吞下20个不透射线的标志测量WGTT,通过乳果糖氢呼吸试验测定OCTT。     

全胃切除Roux—Y食管空肠吻合术后小肠运动功能研究

目的研究全胃切除食管空肠吻合病人的小肠运动生理与排空功能。方法应用小肠多点持续式灌注侧压研究１０例全胃切除病人的Ｒｏｕｘ肠运动；核素显像测量小肠排空时间，并与１２例Ｂ－Ⅱ式远端胃大部切除病人和７例正常人相比较。结果正常对照、胃大部及全胃切除组的口－结肠时间（ＭＣＴＴ）分别为：１９７±７．５９．２０２．５８±８．６６及２３７．２２±９．４６（分钟），差异有显著性（Ｆ＝５．５２，Ｐ＜０．０５），提示全胃切除Ｒｏｕｘ－Ｙ食管空肠吻合可能延缓小肠食物传递；空肠Ｒｏｕｘ肠袢试餐半排空时间为：８．３±３．４３（分钟）。Ｒｏｕｘ肠袢运动均有不同程度异常。表现消化间期ＭＭＣ活动缺乏，逆向传播等；消化期运动削弱，个别异常小肠收缩波引起餐后腹痛。结论全胃切除Ｒｏｕｘ－Ｙ食管空肠吻合可诱发Ｒｏｕｘ肠运动紊乱，但不妨碍食物通过该肠袢，而严重者与餐后不适相关。     

乳果糖氢呼吸试验测定口-盲肠传递时间

目的测定功能性消化不良（ＦＤ）和肠易激综合征（ＩＢＳ）患者口－盲肠传递时间（ＯＣＴＴ）．方法应用乳果糖氢呼吸试验（ＬＨＢＴ）测定了正常人１３例，ＦＤ２０例和ＩＢＳ（其中１５例主诉腹泻，１６例主诉便秘）３１例患者的ＯＣＴＴ．结果正常人ＯＣＴＴ为９５４±１９６ｍｉｎ，ＦＤ患者（９９２±２４５ｍｉｎ）与正常人比较无显著性差异（Ｐ＞００５），但其中５例动力障碍型ＦＤ的ＯＣＴＴ则显著延长（１２９０±１２０ｍｉｎ，Ｐ＜００１），以便秘为主的ＩＢＳ患者ＯＣＴＴ显著延长（１５４４±５５７ｍｉｎ，Ｐ＜００１），以腹泻为主的ＩＢＳ患者ＯＣＴＴ显著缩短（７３１±２２２ｍｉｎ，Ｐ＜００５）．结论ＦＤ和ＩＢＳ患者存在小肠动力学异常，ＬＨＢＴ可作为辅助检查小肠动力学异常的手段之一．     

左旋精氨酸对吸入一氧化氮降低肺动脉高压的延长作用

目的观察一氧化氮底物左旋精氨酸（Ｌａｒｇ）延长吸入一氧化氮（ＮＯ）选择性降低肺动脉高压过程中的作用。方法８只猪麻醉后制成急性缺氧性肺动脉高压模型，在ＳｗａｎＧａｎｚ导管和动脉导管监测下吸入ＮＯ（１２～１５ｐｐｍ）的过程中静脉注入Ｌａｒｇ（共１０ｇ），观察停用ＮＯ后体循环和肺循环血流动力学的变化情况。结果单纯吸入ＮＯ能选择性降低急性缺氧性肺动脉高压，肺动脉压力从４２±０４ｋＰａ降至２５±０５ｋＰａ（１ｋＰａ＝７．５ｍｍＨｇ，Ｐ＜０．０１），肺血管阻力从５６±２５ｋＰａ·ｓ·Ｌ１降至３１±１３ｋＰａ·ｓ·Ｌ－１（Ｐ＜０．０１），但持续时间短；ＮＯ吸入加静脉注射Ｌａｒｇ没有使肺动脉压进一步下降，但能显著延长吸入ＮＯ对肺动脉压的降压时间（２０倍），对体循环血压则无影响。结论提供内源性ＮＯ的底物Ｌａｒｇ能延长ＮＯ的降压作用，提示急性缺氧时ＮＯ的生成可能有相对不足。     

抗抑郁药治疗肠易激综合征的研究进展

目前研究发现精神心理因素在肠易激综合征（IBS）的发病中起重要作用,抗抑郁药在治疗IBS中的作用已受到越来越多的关注。常用的抗抑郁药包括选择性5-羟色胺再摄取抑制剂（SSRIs）、三环类抗抑郁药（TCAs）、5-羟色胺和去甲。肾上腺素再摄取抑制剂（SNRIs）等。本文就近年抗抑郁药治疗IBS的研究进展作一综述。     

化疗药物和昂丹司琼对术后化疗病人小肠动力的影响

对化疗药物在导致恶心和呕吐等副作用的同时可加快小肠动力的研究，目前仅限于不多的动物实验，而临床研究未见报道。５羟色胺（５ＨＴ）３受体阻断剂昂丹司琼（ｏｎｄａｎｓｅｔｒｏｎ，枢复宁）在阻断化疗病人呕吐的同时是否也影响小肠动力尚未见报道。本研究旨在了解病人应用化疗药物前后小肠动力变化，昂丹司琼对呕吐和小肠动力的影响及其间的关系。对象和方法１４例４１～５７岁结直肠癌术后化疗病人，其中男７例，女７例。实验前晚经鼻置入测压管，晨起后在Ｘ线透视下确定并调整导管位置使其至少有两导进入小肠。然后采用Ｐｏｌｙ…     

小肠移植的内镜监测

目的探讨内镜在小肠移植监测中的作用．方法动物实验，白色杂种猪行异体节段性小肠移植，移植小肠行ＴｈｉｒｙＶｅｌａ造口，由内镜通过肠造口观察应用（ｎ＝６）和未应用（ｎ＝６）免疫抑制剂移植小肠粘膜变化．临床研究，一女性短肠综合征患者接受异体全小肠移植，由内镜通过肠造口定时观察移植小肠．结果小肠移植排斥的内镜表现为局灶性肠粘膜红斑、糜烂和溃疡．弥漫性溃疡伴出血是排斥的晚期表现．结论内镜观察是小肠移植必需的监测手段．     

山梨醇氢呼气试验测定口─盲肠通过时间及西沙比利对其影响的研究

目的对山梨醇氢呼气试验测定口─盲肠通过时间进行方法学研究，并观察西沙比利对健康人及患者口─盲肠通过时间的影响。方法以不同剂量的山梨醇作为试验糖并与泛影葡胺放射学方法进行对照。结果１５ｇ山梨醇的产氢率较高，副作用较少。山梨醇呼气氢试验测得的口─盲肠通过时间与泛影葡胺放射学方法的结果之间有显著的相关性（ｒ＝０．９１９）。十二指肠球部溃疡、慢性胃窦炎、肝硬化及糖尿病患者口─盲肠通过时间与正常对照组比较，差异有非常显著性（Ｐ均＜０．００１），服用西沙比利（１０ｍｇ，三次／日×３天），正常对照者、十二指肠球部溃疡、肝硬化及糖尿病患者口─盲肠通过时间显著缩短（Ｐ均＜０．００１）。结论（１）山梨醇呼气氢试验是简易、可靠、重复性好及非创伤性的测定口─盲肠通过时间的方法；（２）西沙比利可以显著缩短十二指肠球部溃疡、肝硬化及糖尿病患者的口─盲肠通过时间，其作用可能与加速胃排空，缩短小肠通过时间有关。     

抗抑郁药物是如何帮助患者的?

正抗抑郁药物可以有助于缓解失眠、食欲不振以及疲劳相关的抑郁症。当医生建议患者服用抗抑郁药物以治疗抑郁症,如选择性5-羟色胺再摄取抑制剂(SSRIs)或者是5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRIs),这不仅是促进改善情绪。抑郁症有很多潜在的身体作用。哈佛附属马萨诸塞州综合医院老年病学专家阿曼达·赫南德兹博士称,大部分人都     

5-Hydroxytryptamine and human small intestinal motility: effect of inhibiting 5-hydroxytryptamine reuptake.

Parenteral 5-hydroxytryptamine stimulates small intestinal motility, but the effect of continuous stimulation with 5-hydroxytryptamine on the human migrating motor complex is unknown. Using a selective 5-hydroxytryptamine reuptake inhibitor, paroxetine, this study investigated the effect of indirect 5-hydroxytryptamine agonism on fasting small intestinal motility and transit. Eight healthy subjects were studied while receiving paroxetine 30 mg daily for five days and while receiving no treatment, in random order. Ambulant small intestinal motility was recorded from five sensors positioned from the duodenojejunal flexure to the ileum for 16-18 hours. Paroxetine reduced the migrating motor complex periodicity mean (SEM) from 81 (6) min to 67 (4) min (p < 0.05), and increased the propagation velocity of phase III from 3.1 to 4.7 cm/min in the proximal jejunum (p < 0.01), and from 1.6 to 3.4 cm/min distally (p < 0.001). Orocaecal transit time measured by lactulose hydrogen breath test was reduced by paroxetine from 70 (9) min to 48 (7) min (p < 0.05). These data suggest that 5-hydroxytryptamine participates in the control of migrating motor complexes in humans, and that selective 5-hydroxytryptamine reuptake inhibitors have a prokinetic action in the human small intestine.     

Stress effects on gastrointestinal transit in the rat.

Previous investigations of stress effects on gastric emptying, orocaecal, and colonic transit in rats have produced conflicting results. Here one type of stressor, a 'passive avoidance' situation, was used to investigate its effects on gastric emptying, orocaecal and colonic transit. After the rats had been trained to eat a standard amount of semisolid food, gastric emptying was determined (n = 12) by the food remaining in the stomach after various periods of rest, or stress exposure. Orocaecal transit (n = 14) was determined by breath hydrogen measurements after the food had been labelled with 1 g lactose. Colonic transit (n = 18) was measured as the arrival time of coloured faeces after infusion of a carmine red solution into the caecum through a chronically implanted catheter. The stressor had differential effects on transit through the stomach, small bowel and colon: gastric emptying was delayed (p less than 0.05) after stress (t1/2 = 2.66 h after stress, 1.97 h at rest). Orocaecal transit was accelerated (p less than 0.05) after stress; transit time decreased from 124.3 min at rest to 86.2 min after stress. Colonic transit was accelerated (p less than 0.01) under stress, from 15.5 h to 1.29 h. It is concluded that gastrointestinal transit in different parts of the gastrointestinal tract is differently affected by central nervous stimuli.     

Severe hepatotoxicity with jaundice associated with paroxetine

Hepatotoxicity due to paroxetine, a selective serotonin reuptake inhibitor, is very rare, and to the best of our knowledge, only five cases of liver injury in association with paroxetine have previously been reported in the medical literature. We describe the clinical, biochemical, and pathological findings in a patient with paroxetine hepatotoxicity, which was reversed after withdrawal of the drug. The present case and the others previously reported suggest that hepatotoxicity should be taken into account as a rare complication, sometimes severe, that may occur with paroxetine.     

Modulation of orocaecal transit time by hypnosis.

The ability of hypnosis to modulate the orocaecal transit time of 10 g lactulose was tested in six healthy volunteers. Orocaecal transit time was measured by the hydrogen breath test during three periods in random order. During the control period the subjects remained throughout the test in a semirecumbent position without moving. During the hypnotic relaxation period subjects were hypnotised before lactulose ingestion and were instructed to experience relaxation till the orocaecal transit time had elapsed. During the acceleration suggestion period subjects were hypnotised before lactulose ingestion and were repeatedly instructed to imagine the acceleration of lactulose through the intestine until transit time had elapsed. The mean orocaecal transit time was significantly longer during the hypnotic relaxation period (mean (SEM) 133 (8) min) than during the control period (93 (13) min). The mean orocaecal transit time during the acceleration suggestion period was 105 (26) minutes and was not significantly different from the mean transit time during the control period. The individual values during the acceleration suggestion period were scattered. We conclude that lactulose orocaecal transit time is delayed during hypnotic relaxation.     

Effects on gastrointestinal functions and symptoms of serotonergic psychoactive agents used in functional gastrointestinal diseases

The effects of antidepressants on the gastrointestinal tract may contribute to their potential efficacy in functional dyspepsia and irritable bowel syndrome; buspirone, a prototype 5-HT1A agonist, enhances gastric accommodation and reduces postprandial symptoms in response to a challenge meal. Paroxetine, a selective serotonin reuptake inhibitor, accelerates small bowel but not colonic transit, and this property may not be relevant to improve gut function in functional gastrointestinal disorders. Venlafaxine, a prototype serotonin norepinephrine reuptake inhibitor, enhances gastric accommodation, increases colonic compliance and reduces sensations to distension; however, it is associated with adverse effects that reduce its applicability in treatment of functional gastrointestinal disorders. Tricyclic antidepressants reduce sensations in response to food, including nausea, and delay gastric emptying, especially in females. Buspirone appears efficacious in functional dyspepsia; amitriptyline was not efficacious in a large trial of children with functional gastrointestinal disorders. Clinical trials of antidepressants for treatment of irritable bowel syndrome are generally small. The recommendations of efficacy and number needed to treat from meta-analyses are suspect, and more prospective trials are needed in patients without diagnosed psychiatric diseases. Antidepressants appear to be more effective in the treatment of patients with anxiety or depression, but larger prospective trials assessing both clinical and pharmacodynamic effects on gut sensorimotor function are needed.     

Tolerance and side-effects of paroxetine in elderly depressed patients

Paroxetine, a selective serotonin reuptake inhibitor (SSRI) antidepressant, is considered to have fewer side-effects than a typical tricyclic antidepressant. As the elderly frequently suffer from adverse effects of psychotropic drugs, safeties and tolerance of paroxetine and their relationship with dose were studied in a double-blind study. Sixteen nondashhospitalised depressed patients, aged 72-86 years, were recruited but 12 patients completed the study. Patients were randomly selected to receive either 15 mg or 30 mg paroxetine daily for 42 days in a double-blind study. A trained nurse made weekly home visits to monitor their medication and general conditions. Patients were assessed at the hospital on days 1, 7, 14, 28 and 42. There were four drop-outs during the first week of study due to lack of motivation, skin rash and upper gastrointestinal symptoms (n=2). Plasma levels of paroxetine showed a dose-related increase in concentrations and indicated a good compliance. At the dosages used, no changes in blood pressure, heart rate, salivary volume, visual choice reaction time, critical flicker fusion threshold and short-term memory were observed in these patients. However, there was a significant improvement in their subjective symptoms (as assessed by a symptom check list and Hamilton Rating Scale) in the 30 mg group, indicating a feeling of well-being.     

Relationship Between the Systems Responsible for Uptake of 5-hydroxytryptamine and of Noradrenaline by Human Blood Platelets

Human blood platelets carry a high affinity, but low capacity, saturable system for the uptake of noradrenalhe. The uptake is partially Na(+) dependent but cannot be categorised as uptake. It is distinct from the uptake system responsible for 5-hydroxytryptamine transport into the platelet since the selective inhibitors of the platelet uptake system for 5-hydroxytryptamine (citalopram, paroxetine) Wer from those for the uptake system for noradrenaline (normetanephrine, methylisoprenaline). 5-hydroxytryptamine inhibits noradrenaline uptake but with properties inconsistent with competition for the same uptake system while noradrenaline does not inhibit 5-hydroxytryptamine uptake. Neither noradrenaline nor 5-hydroxytryptamine uptake by human platelets is inhibited by dopamine.     

Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder

BACKGROUND & AIMS: Prucalopride (PRU) is a selective benzofuran 5-hydroxytryptamine(4)-receptor agonist with gastrointestinal and colonic prokinetic activities. We evaluated the effects of PRU on gastrointestinal and colonic transit in patients with constipation. METHODS: Gastrointestinal and colonic transit were measured over 48 hours in 40 patients who fulfilled modified Rome I criteria for functional constipation. Patients had no evidence of a rectal evacuation disorder. Subjects were randomized to receive a daily dose of 2 or 4 mg PRU or placebo in a double-blind, parallel-group design. Each treatment lasted 7 days. The transit test was performed over the last 48 hours of the study. Effects on gastric emptying, small bowel transit, and colonic transit were analyzed using Kruskal-Wallis and Wilcoxon rank sum tests. RESULTS: Of 61 patients screened, 40 were eligible and randomized. Two patients withdrew because of adverse events. PRU accelerated overall gastric emptying and small bowel transit. PRU tended to accelerate overall colonic transit with significantly faster overall colonic transit and ascending colon emptying with the 4-mg dose. CONCLUSIONS: PRU accelerates transit through the stomach, small bowel, and colon in patients with constipation unassociated with a rectal evacuation disorder.     

帕罗西汀治疗肠易激综合征患者的情绪障碍及腹部症状

探讨选择性５－羟色胺现摄取抑制剂（ＳＳＲＩ）帕罗西汀治疗肠易激综合征（ＩＢＳ）的疗效,以及ＩＢＳ患者精神症状与腹部症状的关系。方法：３６例有精神障碍表现的ＩＢＳ患者服用幅罗西汀治疗８周,治疗前后分别对患者行汉密尔顿抑郁量表（ＨＡＭＤ）、汉密尔顿焦虑量表（ＨＡＭＡ）和胃肠道症状计分标准（ＧＳＲＳ）评分并分析３种 发的相关性。结果：ＩＢＳ患者服用帕罗西汀治疗前后的ＨＡＭＤ、ＨＡＭＡ和ＧＳＲＳ评分存在显     

Effect of selective 5HT3 antagonist (GR 38032F) on small intestinal transit and release of gastrointestinal peptides

Antagonists of 5-hydroxytryptamine type 3 (5HT₃) receptors reduce the nausea induced by cisplatinum, but the effects of these agents on 5HT₃ receptors in the human gut remain to be defined. We examined the actions of one of these drugs (Glaxo GR 38032F) on small intestinal transit and mouth-to-cecum transit times in healthy man. We also quantified its effects on the release of peptide YY (PYY), neurotensin, human pancreatic polypeptide, gastrin-cholecystokinin, and motilin. Ten healthy volunteers were enrolled in a randomized, double-blind, placebo-controlled crossover study. Following a single intravenous dose of GR 38032F (0.15 mg/kg), we measured the time to appearance in plasma of sulfapyridine after injection of salicylazosulfapyridine into the duodenum. This was used as a measure of duodenocecal transit. The appearance of hydrogen in breath after ingestion of a meal containing lactulose was also correspondingly used to quantify the mouth-to-cecum transit of the head of the meal. Gastrointestinal hormones were assayed in plasma by specific RIAs; samples were drawn fasting (10 min after injection) and after breakfast (358 calories: 15.7 g protein, 55.4 g carbohydrate, 8.1 g fat). The postprandial integrated response and peak release of PYY was decreased by GR 38032F. There was also a trend for the peak release of neurotensin to be reduced. GR 38032F did not significantly alter small intestinal transit times or mouth-to-cecum transit times. We conclude that GR 38032F does not have a major effect on small intestinal transit in health.Supported in part by grants from Glaxo Inc., USA, and from the National Institutes of Health (RR585, DK34988, and DK32121).