• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Internet Journal of Pharmacology >Buspirone And Anxiety Disorders: A Review With Pharmacological And Clinical Perspectives
【24h】

Buspirone And Anxiety Disorders: A Review With Pharmacological And Clinical Perspectives

机译：丁螺环酮和焦虑症：药理学和临床观点的回顾

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The treatment of anxiety is one of the leading problems in medicine today. Buspirone, an azpirone derivative and a 5-HT-1A (5-hydroxytryptamine-1A) partial agonist, is the first nonbenzodiazepine anxiolytic introduced into medicine for the treatment of generalized anxiety disorder (GAD). It has a strong affinity for the 5-HT-1A receptor and does not appear to interact at the benzodiazepine receptor complex. Buspirone's distinctive mechanism of action helps to avoid pharmacological properties ancillary to the treatment of anxiety and contributes towards an apparently superior safety profile with generally fewer and more tolerable adverse effects than benzodiazepines. This article provides a brief overview on the results of animals and clinical studies in which the potential for buspirone dependence or abuse and the effects of its withdrawal were assessed. The pharmacology of serotonin systems and its role in the management of anxiety, along with the review of the contemporary literature is also discussed. Introduction A role of central serotonin (5-hydroxytryptamine; 5-HT) in the pathogenesis of anxiety has been the subject of intensive research. Experimental evidence based primarily on drug therapy suggests that anxiolytic effects of benzodiazepines (BZs), the conventional anxiolytics, are manifested by the stimulation of BZ-GABA (Gamma amino butyric acid) receptor complex and a concomitant decrease in serotonergic neuronal activity 1,2 . Despite a trend of reduced prescribing the BZs remain the most widely used psychotropic drugs and this is due to their considerable effectiveness as anxiolytic 3 , hypnotic 4 and anticonvulsant 5 . Although a large number of different BZs exist, they share a common property of binding with a high affinity to specific recognition sites in brain 6 . Drugs that tend to increase 5-HT functions are anxiogenic while blockade of serotonergic neurotransmission produced anti-anxiety effects. Serotonergic hypothesis of anxiety is complicated by recent awareness of heterogeneity of 5-HT receptors in the central nervous system 7 . The advent of selective agonists and antagonists for 5-HT receptor subtypes has rekindled investigation of the role of 5-HT in anxiety mechanisms 8 .Serotonin agonists with selectivity towards 5-HT-1A sites have been shown to release suppression of behaviour in models of anxiety 9,10 . These drugs decreased 5-HT turnover in rat brain 11,12,13 . Serotonergic cell groups of the median raphe nucleus innervating the hippocampus have an important role in the anxiety mechanisms. Brain hippocampus, an important site of BZ action, possessing high density of 5-HT-1A binding sites 14,15 . Pharmacological studies show that decreasing the availability of 5-HT at postsynaptic 5-HT-2A or 5-HT-2C sites is anxiolytic 16,17,18 . 5-HT-1A agonists such as buspirone, ipsapirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) showed anxiolytic profile 19,20 . This may be due to their potent agonistic activity towards cell body autoreceptors 21 . Since they reduce serotonin neural function by suppressing neuronal firing. It has been proposed that this is the basis of their anxiolytic action 22 . Unlike the BZs, 5-HT-1A agonists have been reported to produce little sedation, do not potentiate the effects of ethanol, and do not show potential for dependence or abuse 19,23 . They do not seem to interact with the GABA-benzodiazepine-Cl ionophore complex 24 . Depression of 5-HT neuron function is, therefore, critically important for therapeutic effects of both 5-HT-1A 25,26 and BZ anxiolytics 27 . Taken together, these observations lead to the conclusion that different 5-HT mechanisms, mediated by different receptor subtypes, are involved in the genesis of anxiety. Anxiety Anxiety is a normal reaction but when it is severe and disabling it becomes pathological 28 . Anxiety is an almost ubiquitous component of mental illnesses. It is present in its purest form in the so-called anxiety disorder
机译：焦虑症的治疗是当今医学中的主要问题之一。丁螺环酮（一种螺环酮衍生物和一种5-HT-1A（5-羟色胺-1A）部分激动剂）是第一种被引入药物中的非苯二氮卓类抗焦虑药，用于治疗广泛性焦虑症（GAD）。它对5-HT-1A受体具有很强的亲和力，在苯二氮杂receptor受体复合物上似乎没有相互作用。丁螺环酮独特的作用机制有助于避免焦虑症治疗所具有的药理特性，并有助于产生明显优于苯并二氮杂卓的安全性，且不良反应通常要少且可忍受。本文简要概述了动物和临床研究的结果，其中评估了丁螺环酮依赖或滥用的可能性以及其停用的影响。还讨论了5-羟色胺系统的药理学及其在焦虑症治疗中的作用，以及对当代文献的回顾。引言中央5-羟色胺（5-羟色胺; 5-HT）在焦虑症发病中的作用已成为深入研究的主题。主要基于药物治疗的实验证据表明，常规的抗焦虑药苯二氮卓类药物（BZs）的抗焦虑作用通过BZ-GABA（γ-氨基丁酸）受体复合物的刺激和血清素神经神经活性1,2的降低而得以体现。尽管开处方的趋势有所减少，但BZ仍然是使用最广泛的精神药物，这是由于它们作为抗焦虑药3，催眠药4和抗惊厥药5的有效性。尽管存在大量不同的BZ，但它们具有对大脑6的特定识别位点具有高亲和力结合的共同属性。趋于增强5-HT功能的药物具有抗焦虑作用，而阻断5-羟色胺能神经传递可产生抗焦虑作用。最近，人们意识到中枢神经系统中5-HT受体的异质性，从而使焦虑的血清素能假说变得更加复杂7。 5-HT受体亚型的选择性激动剂和拮抗剂的出现重新点燃了对5-HT在焦虑机制中的作用的研究8。对5-HT-1A位点具有选择性的5-羟色胺激动剂已在模型中释放出对行为的抑制。焦虑9,10。这些药物降低了大鼠大脑11,12,13的5-HT转化率。支配海马的正中缝核的血清素能细胞群在焦虑机制中具有重要作用。脑海马，BZ作用的重要部位，拥有5-HT-1A结合位点14,15的高密度。药理研究表明，降低5-HT在突触后5-HT-2A或5-HT-2C部位的可用性是抗焦虑的16,17,18。 5-HT-1A激动剂，例如丁螺环酮，依普西隆和8-羟基-2-（二-正丙基氨基）四氢化萘（8-OH-DPAT）显示抗焦虑性19,20。这可能是由于它们对细胞体自身受体21的有效激动作用。由于它们通过抑制神经元放电而降低了血清素的神经功能。已经提出，这是其抗焦虑作用的基础22。不同于BZs，据报道5-HT-1A激动剂几乎不会产生镇静作用，不会增强乙醇的作用，也没有表现出依赖性或滥用的潜力19,23。他们似乎不与GABA-苯二氮杂-Cl离子载体复合物相互作用24。因此，5-HT神经元功能的降低对于5-HT-1A 25,26和BZ抗焦虑药27的治疗作用至关重要。综上所述，这些观察得出的结论是，由不同的受体亚型介导的不同的5-HT机制参与了焦虑的发生。 焦虑焦虑是一种正常的反应，但是当严重且致残时，就会变成病理28。焦虑是精神疾病中几乎普遍存在的成分。它以最纯净的形式存在于所谓的焦虑症中

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号