Gorman Jack M
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Clin Psychiatry. 2003;64 Suppl 3:28-35.
Recent advances in neuroscience and understanding in the etiology of anxiety have led researchers to new targets for treatments that are proving to be at least as effective as benzodiazepines, which have been the traditional treatment for anxiety for over 40 years. The gamma-aminobutyric acid (GABA) system has long been targeted in anxiety interventions via benzodiazepines, but better understanding of its role in anxiety disorders has led to the development of partial benzodiazepine-GABA receptor antagonists and agents that target specific subunits of the GABA-A receptor and that manipulate GABA levels. The recognition that antidepressants are effective in anxiety even in nondepressed patients has caused researchers to develop antianxiety agents that affect the serotonin and norepinephrine systems. Other neurotransmitter systems such as corticotropin-releasing factor and substance P appear to be abnormally regulated in patients with anxiety disorders, so antagonists of these neurotransmitters may prove to be beneficial anxiolytics. Meanwhile, antistress and antianxiety effects through neurogenesis may be possible with the use of agents that decrease glutamate neurotransmission, such as metabotropic glutamate receptor agonists. Finally, the stimulation of neurotrophic factors, such as brain-derived neurotrophic factor, which appears to enhance neurogenesis, may also prove to have anxiolytic effects.
神经科学的最新进展以及对焦虑症病因的深入理解，促使研究人员找到了新的治疗靶点，这些靶点已被证明至少与苯二氮䓬类药物一样有效，而苯二氮䓬类药物在过去40多年里一直是治疗焦虑症的传统药物。长期以来，γ-氨基丁酸（GABA）系统一直是通过苯二氮䓬类药物进行焦虑干预的靶点，但对其在焦虑症中作用的更深入了解，促使人们开发出了部分苯二氮䓬-GABA受体拮抗剂以及靶向GABA-A受体特定亚基并调节GABA水平的药物。认识到抗抑郁药即使对非抑郁症患者的焦虑症也有效，这促使研究人员开发出影响血清素和去甲肾上腺素系统的抗焦虑药物。其他神经递质系统，如促肾上腺皮质激素释放因子和P物质，在焦虑症患者中似乎存在异常调节，因此这些神经递质的拮抗剂可能被证明是有益的抗焦虑药。同时，使用减少谷氨酸神经传递的药物，如代谢型谷氨酸受体激动剂，可能通过神经发生产生抗应激和抗焦虑作用。最后，刺激神经营养因子，如脑源性神经营养因子，似乎可以增强神经发生，这也可能被证明具有抗焦虑作用。
