Zwanzger Peter, Rupprecht Rainer
Anxiety Research Unit and Anxiety Outpatient Clinic, Department of Psychiatry, Ludwig-Maximilians-Universität, Munich, Germany.
J Psychiatry Neurosci. 2005 May;30(3):167-75.
gamma-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system (CNS). It exerts its rapid inhibitory action mostly through GABA(A) receptors, which are targets for benzodiazepines, barbiturates, neuroactive steroids and distinct anticonvulsive agents. There is considerable evidence that dysfunction of GABA(A) receptors or dysregulation of GABA concentrations in the CNS (or both) plays an important role in the pathophysiology of panic disorder. Currently, benzodiazepines are the only drugs directly targeting the GABA(A) receptors that are approved for the treatment of anxiety disorders. Because of their well-known anxiolytic effects, they are widely used in this setting, but side effects limit their use in long-term treatment. The question of whether drugs that selectively increase GABA concentrations in the CNS could improve symptoms of anxiety has been discussed. Recent investigations by our group have demonstrated that enhancement of endogenous GABA (through blockade of GABA transaminase by vigabatrin or through inhibition of GABA transporters by tiagabine) exerts anxiolytic effects on experimentally induced panic. Our studies in healthy volunteers have shown that both compounds lead to a significant reduction in panic symptoms elicited by cholecystokinin-tetrapeptide. Moreover, benzodiazepine-like effects on the activity of the hypothalamic-pituitary-adrenal axis have been observed in association with vigabatrin treatment. Small open studies in patients with panic disorder also showed an improvement in panic and anxiety with both compounds. This review summarizes our recent research on the effects of selective GABAergic treatment in experimentally induced panic and outlines the possible role of compounds targeting the GABA binding site of the GABA(A)-benzodiazepine receptor for the treatment of panic and anxiety.
γ-氨基丁酸（GABA）是中枢神经系统（CNS）中最重要的抑制性神经递质。它主要通过GABA（A）受体发挥快速抑制作用，而GABA（A）受体是苯二氮䓬类药物、巴比妥类药物、神经活性甾体及不同抗惊厥药物的作用靶点。有大量证据表明，GABA（A）受体功能障碍或中枢神经系统中GABA浓度失调（或两者兼有）在惊恐障碍的病理生理学中起重要作用。目前，苯二氮䓬类药物是唯一被批准用于治疗焦虑症的直接靶向GABA（A）受体的药物。由于其众所周知的抗焦虑作用，它们在这种情况下被广泛使用，但副作用限制了它们在长期治疗中的应用。关于选择性增加中枢神经系统中GABA浓度的药物是否能改善焦虑症状的问题已被讨论。我们小组最近的研究表明，增强内源性GABA（通过氨己烯酸阻断GABA转氨酶或通过噻加宾抑制GABA转运体）对实验诱导的惊恐具有抗焦虑作用。我们在健康志愿者中的研究表明，这两种化合物都能显著减轻胆囊收缩素四肽引起的惊恐症状。此外，与氨己烯酸治疗相关的下丘脑-垂体-肾上腺轴活性的苯二氮䓬样作用也已被观察到。对惊恐障碍患者的小型开放研究也表明，这两种化合物都能改善惊恐和焦虑症状。这篇综述总结了我们最近关于选择性GABA能治疗对实验诱导的惊恐的影响的研究，并概述了靶向GABA（A）-苯二氮䓬受体GABA结合位点的化合物在治疗惊恐和焦虑中的可能作用。
