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1.
王申捷  孙凡  朱亮 《生物磁学》2014,(3):571-574
5-羟色胺(5-hydroxy tryptamine,5-HT)是中枢及外周神经系统中一种重要的神经递质。5-羟色胺转运体(5-HT transporter,5-HTT)可将5.HT再摄取,降低细胞外5-HT浓度,从而调节神经信号传导。5-HTT异常在某些精神疾病的发病中起重要作用。近年来选择性5.羟色胺再摄取抑制剂(selective serotonin reuptake inhibitors,SSRIs)在临床上的应用日趋广泛,如治疗抑郁症、焦虑症、抑郁和焦虑共病等常见的精神疾病。氟西汀、帕罗西汀、舍曲林、氟伏沙明和西酞普兰是目前临床上最常用的五种SSRIs,被誉为抗抑郁药的“五朵金花”。本文详细介绍近年来在临床上药物治疗抑郁症取得的成果以及这类药物的药效学、药动学、不良反应和相互作用等,并简要介绍SSRIs在其它疾病领域取得的应用进展。  相似文献   

2.
抑郁症是一种发病率高、危害大的精神疾病,且发病的人群正在急剧增加。抑郁症的成因复杂,其病因机制尚不十分清楚。目前研究的病因主要包括神经递质受体异常、神经退化及内分泌、炎症细胞因子、表观遗传调节和大脑衍生神经营养因子等。随着新病因的揭开,抑郁症治疗的新药及其作用机理研究也取得了较大的进展。研发的新药主要包括:选择性5-羟色胺(5-HT)、去甲肾上腺素(NE)再摄取抑制剂、选择性NE再摄取抑制剂、肾上腺素能和特异性5-HT抗抑郁药、以及新药氯胺酮。本文就抑郁症发病的成因及主要的新药治疗策略进行了综述,为揭示抑郁症致病机制及其新药研发提供了理论依据。  相似文献   

3.
五羟色胺转运体是一种对五羟色胺(5-HT,serotonin)有高度亲和力的跨膜转运蛋白,能够重新摄取细胞间隙内的5-HT,从而调节神经信号的转导。该文简述了五羟色胺转运体的生物学特性、分布以及与人类疾病的关系,通过分析比较发现,五羟色胺转运体的多态性与肠易激综合征、抑郁症、强迫症都有着密切的关系。  相似文献   

4.
5-羟色胺系统与抑郁症关系密切,阐明5-羟色胺相关受体在抑郁症中的作用,有助于抗抑郁药物的开发与应用,提高抑郁症的治疗效果。在5-羟色胺的受体中,5-羟色胺2C受体(5-hydroxytryptamine type 2C receptor,5-HT2CR)在抑郁症的发病及治疗机制中发挥重要的作用。虽然已有关于5-羟色胺2C受体与抑郁症具有相关性的报道,但近年来,5-羟色胺2C受体参与抑郁症的相关分子机制有了新的进展,本文将抑郁症分子机制中5-羟色胺2C受体的作用加以综述,以期为相关工作提供依据。  相似文献   

5.
γ-氨基丁酸(γ-aminobutyric acid,GABA)是哺乳动物中枢神经系统中主要的抑制性神经递质,与焦虑、抑郁、精神分裂等多种神经和精神疾病有关。近年来,越来越多的研究提示,抑郁症的发生与中枢GABA功能缺陷密切相关。但目前基于单胺类递质失调及谷氨酸能神经的研究较多,而对GABA的研究相对较少且比较分散。本文主要通过介绍GABA受体及其作用,以及GABA与5-羟色胺(5-hydroxytryptamine,5-HT)、多巴胺(dopamine,DA)和谷氨酸(glutamic acid,Glu)的相互作用,讨论GABA与抑郁症发生的关系,以期为抑郁症的发生机制与治疗的深入研究提供思路。  相似文献   

6.
5-羟色胺转运体(5-HTT)在神经精神心理正常功能的维持及疾病的发生和发展中起重要作用。5-HTT的表达能力减低或消失的小鼠(称为:5-HTT敲除小鼠)表现出许多行为的改变,例如:焦虑类似行为增多、对应激更加敏感和攻击性行为减少。这些行为的改变有的与携带5-HTTLPR短等位基因的人很相似。因此5-HTT敲除小鼠被作为研究5-HTTLPR多态性导致情感性精神障碍发病机制的动物模型。本文主要就5-HTT敲除小鼠的5-HT浓度和代谢、下丘脑-垂体-肾上腺皮质轴以及对其他神经递质转运体影响的分子和细胞改变进行综述。  相似文献   

7.
本实验通过豚鼠离体肠系膜下神经节(IMG)的细胞内生物电记录方法观察到:(1)5-羟色胺(5-HT 1-100μmol/L)灌流可在部分 IMG 细胞引起与非胆碱能迟慢兴奋性突触后电位(Is-EPSP)相似的缓慢去极化;(2)持续灌流5-HT 可使对5-HT 敏感的 IMG 细胞的Is-EPSP 明显阻抑;(3)5-HT 去极化及5-HT 敏感细胞的 Is-EPSP 均可为5-HT 再摄取抑制剂氟苯氧丙胺(50μmol/L)所增大,而对5-HT 不敏感细胞的 Is-EPSP 则不受这种药物的影响,(4)5-HT 合成抑制剂对氯苯丙氨酸(PCPA)预处理可使 IMG 细胞的 Is-EPSP 的出现率和去极幅度均明显减低。上述结果表明:5-HT 可能参与介导豚鼠部分 IMG 细胞的Is-EPSP。  相似文献   

8.
<正>抑郁症是一种常见的高复发、高致残性精神疾病,其主要表现是情绪低落、丧失兴趣或享受感,并可伴有焦虑症状、认知功能损害、睡眠和食欲紊乱等,已成为一种不容被忽视的全球健康危机[1].据世界卫生组织调查显示,全球抑郁症患者高达3.5亿.我国成年人群抑郁症的终生患病率是6.8%,总体呈上升趋势,已成为我国第二大疾病负担[2].经典的单胺假说认为,单胺类神经递质(包括5-羟色胺(5-hydroxytryptamine,5-HT)、去甲肾上腺素(norepinephrine, NE)和多巴胺)的缺乏是导致抑郁发生的重要病因[3].目前临床上常用的抗抑郁药物的机制也主要是抑制单胺降解或者阻止单胺再摄取,但存在起效时间缓慢、对约30%~50%的患者无效或疗效不佳的局限性,这提示可能存在其他病理机制参与单胺失调和抑郁发生.  相似文献   

9.
目的:通过检测儿童强迫症、抑郁症患者血小板5-羟色胺(5-HT)的浓度,探讨血小板5-HT在儿童强迫症、抑郁症发病中的作用.方法:采用高效液相色谱法检测22例强迫症患儿(包括强迫思维15例,强迫动作7例)和20例抑郁症惠儿血小板5-HT的浓度,并与20名正常儿童进行比较.结果:强迫症患儿(173.43±90.67)ng/109和抑郁症患儿(251.62±152.72)ng/109血小板5-HT的浓度低于正常儿童(351.91±170.97)ng/109(P<0.05),强迫症患儿的血小板5-HT的浓度和抑郁症惠儿的差异没有显著性(P>0.05).强迫症患儿中,强迫思维惠儿的血小板5-HT的浓度(147.09±44.92)ng/109低于强迫动作患儿(229.88±1:136.44)ng/109(P<0.05).结论:儿童强迫症、抑郁症患者血小板5-HT浓度明显下降,并且强迫思维患儿的血小板5-HT浓度与强迫动作患儿的差异有显著性.  相似文献   

10.
目的:探讨难治性抑郁症患者抗抑郁剂治疗前后的单胺类神经递质代谢产物的改变。方法:随机入组30例难治性抑郁症患者,进行汉密尔顿抑郁量表(HAMD)的临床评定。用酶联免疫吸附方法对这30例患者进行5-HIAA,MHPG检测,并与随机选取的经汉密尔顿抑郁量表(HAMD)临床评定的30名普通抑郁症患者进行比较。综合治疗8周后对难治性抑郁症患者进行治疗前后对比。结果:难治性抑郁症组治疗前血浆5-HIAA,MHPG浓度低于普通对照组(p<0.05),经5-羟色胺重摄取抑制剂治疗的难治性抑郁症患者,5-HIAA和MHPG含量与治疗前比较均有所升高,差异有显著性(p<0.05);结论:难治性抑郁症患者存在中枢5-羟色胺和去甲肾上腺素功能低下;个体化合理使用SSRIs类药物辅以心理治疗能有效地提高难治性抑郁症患者的外周单胺类递质水平,减轻患者的抑郁程度。  相似文献   

11.
The regulation of bone metabolism continues to be an area of intense investigation, with recent evidence indicating a potential contribution from the neural system. In particular, the neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) has been hypothesized to play a role in skeletal metabolism via its transporter (5-HTT). The 5-HTT is a plasma membrane transporter that is highly specific for the uptake of extracellular 5-HT, thereby facilitating the intracellular storage and/or degradation of 5-HT. The 5-HTT is clinically important as it is the key target of pharmaceutical agents aimed at treating affective disorders, such as major depressive disorder. By antagonizing the 5-HTT, selective serotonin reuptake inhibitors (SSRIs) potentiate 5-HT activity and effectively relieve the symptoms of depression. However, questions have been raised regarding the potential skeletal effects of SSRIs given the recent identification of a functional 5-HTT and functional 5-HT receptors in bone cells. This paper discusses the preclinical evidence for the skeletal effects of 5-HT and the inhibition of the 5-HTT. In particular, it discusses the: (1) role of 5-HT and the function of the 5-HTT; (2) presence of functional 5-HTTs in bone; (3) potential sources and response mechanisms for 5-HT in bone, and; (4) in vitro and in vivo skeletal effects of 5-HT and 5-HTT inhibition.  相似文献   

12.
The discovery of a functional serotonin (5-hydroxytryptamine; 5-HT) transporter (5-HTT) in bone has given rise to questions about the physiologic role of 5-HT in bone, and the possible clinical implications for humans. 5-HT is known to play a role in the pathophysiology of depression, and many antidepressant medications function by inhibiting the 5-HTT. Among the antidepressants, those that selectively block the 5-HTT (namely, selective serotonin reuptake inhibitors; SSRIs) appear to have skeletal effects. Several studies have demonstrated lower bone density, increased rates of bone loss at the hip, and increased rates of fracture among older individuals taking SSRIs. However, there remains uncertainty about whether it is the antidepressant medications themselves or the reason for their use (depression) that is responsible for these observed bone changes. This paper reviews the epidemiologic literature that explores the role of the 5-HTT in bone health, by looking at questions about how depression, antidepressant therapy and SSRIs impact bone health in humans. Further research will be important to better understand how these factors interact to influence skeletal status, and to characterize the biochemical mechanism through which 5-HT may mediate bone turnover and metabolism.  相似文献   

13.
The antidepressant selective serotonin transporter inhibitors (SSRIs) are clinically active after a delay of several weeks. Indeed, the rapid increase of serotonin (5-HT) caused by SSRIs, stimulates the 5-HT(1A) autoreceptors, which exert a negative feedback on the 5-HT neurotransmission. Only when autoreceptors are desensitized, can SSRIs exert their therapeutic activity. The 5-HT(1A) receptor antagonist pindolol has been used to accelerate the clinical effects of antidepressant by preventing the negative feedback. Using the alpha-[(11)C]methyl-L-tryptophan/positron emission tomography (PET), the goal of the present double-blind, randomized study was to compare the changes in alpha-[(11)C]methyl-L-tryptophan trapping, an index of serotonin synthesis, in patients suffering from unipolar depression treated with the SSRI citalopram (20 mg/day) plus placebo versus patients treated with citalopram plus pindol (7.5 mg/day). PET and Hamilton depression rating scale (HDRS-17) were performed at baseline, and after 10 and 24 days of antidepressant treatment. Results show that the combination citalopram plus pindol, compared to citalopram alone shows a more rapid and greater increase of an index of 5-HT synthesis in prefrontal cortex (BA 9). This research is the first human PET study demonstrating that, after 24 days, the combination SSRIs plus pindolol produces a greater increase of the metabolism of serotonin in the prefrontal cortex, an area associated to depressive symptoms.  相似文献   

14.
The development of selective serotonin reuptake inhibitors (SSRIs) provided a major advancement in the treatment of depression. However, these drugs suffer from a variety of drawbacks, most notably a delay in the onset of efficacy. One hypothesis suggests that this delay in efficacy is due to a paradoxical decrease in serotonergic (5-HT) neuronal impulse flow and release, following activation of inhibitory presynaptic 5-HT1A autoreceptors, following acute administration of SSRIs. According to the hypothesis, efficacy is seen only when this impulse flow is restored following desensitization of 5-HT1A autoreceptors and coincident increases in postsynaptic 5-HT levels are achieved. Clinical proof of this principal has been suggested in studies that found a significant augmenting effect when the beta-adrenergic/5-HT1A receptor antagonist, pindolol, was coadministered with SSRI treatment. In this article, we review preclinical electrophysiological and microdialysis studies that have examined this desensitization hypothesis. We further discuss clinical studies that utilized pindolol as a test of this hypothesis in depressed patients and examine preclinical studies that challenge the notion that the beneficial effect of pindolol is due to functional antagonism of the 5-HT1A autoreceptors.  相似文献   

15.
Depression is characterized by sadness, purposelessness, irritability, and impaired body functions. Depression causes severe symptoms for several weeks, and dysthymia, which may cause chronic, low-grade symptoms. Treatment of depression involves psychotherapy, medications, or phototherapy. Clinical and experimental evidence indicates that an appropriate diet can reduce symptoms of depression. The neurotransmitter, serotonin (5-HT), synthesized in the brain, plays an important role in mood alleviation, satiety, and sleep regulation. Although certain fruits and vegetables are rich in 5-HT, it is not easily accessible to the CNS due to blood brain barrier. However the serotonin precursor, tryptophan, can readily pass through the blood brain barrier. Tryptophan is converted to 5-HT by tryptophan hydroxylase and 5-HTP decarboxylase, respectively, in the presence of pyridoxal phosphate, derived from vitamin B6. Hence diets poor in tryptophan may induce depression as this essential amino acid is not naturally abundant even in protein-rich foods. Tryptophan-rich diet is important in patients susceptible to depression such as certain females during pre and postmenstrual phase, post-traumatic stress disorder, chronic pain, cancer, epilepsy, Parkinson’s disease, Alzheimer’s disease, schizophrenia, and drug addiction. Carbohydrate-rich diet triggers insulin response to enhance the bioavailability of tryptophan in the CNS which is responsible for increased craving of carbohydrate diets. Although serotonin reuptake inhibitors (SSRIs) are prescribed to obese patients with depressive symptoms, these agents are incapable of precisely regulating the CNS serotonin and may cause life-threatening adverse effects in the presence of monoamine oxidase inhibitors. However, CNS serotonin synthesis can be controlled by proper intake of tryptophan-rich diet. This report highlights the clinical significance of tryptophan-rich diet and vitamin B6 to boost serotonergic neurotransmission in depression observed in various neurodegenerative diseases. However pharmacological interventions to modulate serotonergic neurotransmission in depression, remains clinically significant. Depression may involve several other molecular mechanisms as discussed briefly in this report.  相似文献   

16.
Maternal use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) is associated with an increased risk for persistent pulmonary hypertension of the newborn (PPHN), but little is known about 5-HT signaling in the developing lung. We hypothesize that 5-HT plays a key role in maintaining high pulmonary vascular resistance (PVR) in the fetus and that fetal exposure to SSRIs increases 5-HT activity and causes pulmonary hypertension. We studied the hemodynamic effects of 5-HT, 5-HT receptor antagonists, and SSRIs in chronically prepared fetal sheep. Brief infusions of 5-HT (3-20 μg) increased PVR in a dose-related fashion. Ketanserin, a 5-HT 2A receptor antagonist, caused pulmonary vasodilation and inhibited 5-HT-induced pulmonary vasoconstriction. In contrast, intrapulmonary infusions of GR127945 and SB206553, 5-HT 1B and 5-HT 2B receptor antagonists, respectively, had no effect on basal PVR or 5-HT-induced vasoconstriction. Pretreatment with fasudil, a Rho kinase inhibitor, blunted the effects of 5-HT infusion. Brief infusions of the SSRIs, sertraline and fluoxetine, caused potent and sustained elevations of PVR, which was sustained for over 60 min after the infusion. SSRI-induced pulmonary vasoconstriction was reversed by infusion of ketanserin and did not affect the acute vasodilator effects of acetylcholine. We conclude that 5-HT causes pulmonary vasoconstriction, contributes to maintenance of high PVR in the normal fetus through stimulation of 5-HT 2A receptors and Rho kinase activation, and mediates the hypertensive effects of SSRIs. We speculate that prolonged exposure to SSRIs can induce PPHN through direct effects on the fetal pulmonary circulation.  相似文献   

17.
Selective serotonin reuptake inhibitors and neuroendocrine function.   总被引:4,自引:0,他引:4  
D K Raap  L D Van de Kar 《Life sciences》1999,65(12):1217-1235
Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are effective drugs for the treatment of several neuropsychiatric disorders associated with reduced serotonergic function. Serotonergic neurons play an important role in the regulation of neuroendocrine function. This review will discuss the acute and chronic effects of SSRIs on neuroendocrine function. Acute administration of SSRIs increases the secretion of several hormones, but chronic treatment with SSRIs does not alter basal blood levels of hormones. However, adaptive changes are induced by long-term treatment with SSRIs in serotonergic, noradrenergic and peptidergic neural function. These adaptive changes, particularly in the function of specific post-synaptic receptor systems, can be examined from altered adrenocorticotrophic hormone (ACTH), cortisol, oxytocin, vasopressin, prolactin, growth hormone (GH) and renin responses to challenges with specific agonists. Neuroendocrine challenge tests both in experimental animals and in humans indicate that chronic SSRIs produce an increase in serotonergic terminal function, accompanied by desensitization of post-synaptic 5-HT1A receptor-mediated ACTH, cortisol, GH and oxytocin responses, and by supersensitivity of post-synaptic 5-HT2A (and/or 5-HT2C) receptor-mediated secretion of hormones. Chronic exposure to SSRIs does not alter the neuroendocrine stress-response and produces inconsistent changes in alpha2 adrenoceptor-mediated GH secretion. Overall, the effects of SSRIs on neuroendocrine function are dependent on adaptive changes in specific neurotransmitter systems that regulate the secretion of specific hormones.  相似文献   

18.
Chronic psychoemotional stress of social defeats produces development of experimental anxious depression in male mice similar to this disorder in humans. 5-HT and 5-HIAA levels, TPH and MAO A activities, 5-HT1A-receptors in different brain areas were investigated at different stages of development of experimental disorder. It has been shown that initial stage (3 days of social stress) is accompanied by increase of 5-HT level in some brain areas. Decreased 5-HIAA levels in the hippocampus, amygdala and nucleus accumbens were discovered at the stage of forming depression (10 days of social stress). Pharmacological desensitisation and decreased number of 5-HT1A-receptors were shown in frontal cortex and amygdala. At the stage of pronounced depression (20 days of stress), there were no differences in 5-HT and 5-HIAA levels in all brain areas (excluding hypothalamus) of depressive animals. However increased number of 5-HT1A-receptors and decreased affinity in amygdala and decreased TPH and MAOA activities in hippocampus were found in depressive mice. Hypofunction of serotonergic system is suggested at the stage of pronounced depression state in animals. Similar processes had place in brain dopaminergic systems. It is concluded that dynamic changes of brain monoaminergic activities accompany the development of anxious depression in animals. Various parameters of monoaminergic systems are differently changed depending on brain area, mediator system and stage of disorder.  相似文献   

19.
We used knockout mice and receptor antagonist strategies to investigate the contribution of the serotonin (5-hydroxytryptamine, 5-HT) 5-HT1B receptor subtype in mediating the effects of selective serotonin reuptake inhibitors (SSRIs). Using in vivo intracerebral microdialysis in awake mice, we show that a single systemic administration of paroxetine (1 or 5 mg/kg, i.p.) increased extracellular serotonin levels [5-HT]ext in the ventral hippocampus and frontal cortex of wild-type and mutant mice. However, in the ventral hippocampus, paroxetine at the two doses studied induced a larger increase in [5-HT]ext in knockout than in wild-type mice. In the frontal cortex, the effect of paroxetine was larger in mutants than in wild-type mice at the 1 mg/kg dose but not at 5 mg/kg. In addition, either the absence of the 5-HT1B receptor or its blockade with the mixed 5-HT1B/1D receptor antagonist, GR 127935, potentiates the effect of a single administration of paroxetine on [5-HT]ext more in the ventral hippocampus than in the frontal cortex. Furthermore, we demonstrate that SSRIs decrease immobility in the forced swimming test; this effect is absent in 5-HT1B knockout mice and blocked by GR 127935 in wild-type suggesting therefore that activation of 5-HT1B receptors mediate the antidepressant-like effects of SSRIs. Taken together these data demonstrate that 5-HT1B autoreceptors appear to limit the effects of SSRI on dialysate 5-HT levels particularly in the hippocampus while presynaptic 5-HT1B heteroreceptors are likely to be required for the antidepressant activity of SSRIs.  相似文献   

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