Mosconi M, Chiamulera C, Recchia G
Medical Directorate, Glaxo, Verona, Italy.
Int J Clin Pharmacol Res. 1993;13(6):331-44.
Benzodiazepines (BDZ), the most popular drug of choice for treating anxiety disorders, present side-effects such as sedation, muscular disorders, abuse liability and synergistic effect with alcohol and CNS depressant drugs. At present, pharmacological research is focusing to find anxiolytic drugs as efficacious as benzodiazepines but without side-effects. This review reports the status of the pharmaceutical research and development on novel drugs for the treatment of anxiety disorders. A close analysis of the items selected by the N5C "Pharmaprojects" search (anxiolytic class) yielded the following classification: A) Drugs interacting with the GABA-A receptor complex, which includes BDZ-like drugs, partial BDZ agonists (beta-carbolines) and drugs interacting with the GABA-A complex through an as yet unidentified mechanism (15 compounds), B) Drugs acting as CCK-B antagonists (5 compounds), C) Drugs interacting with serotonergic function (30 compounds) subdivided into: (i) agonists at the 5-HT1A receptor, (ii) antagonists at the 5-HT2 receptor, and (iii) antagonists at the 5-HT3 receptor; D) Drugs with other mechanisms (22 compounds). Based on these results, it is not possible to identify a common mechanism through which the selected drugs under development exert their anxiolytic effect. Therefore, it appears that different biological mechanisms are specifically involved in the different anxiety disorders.
苯二氮䓬类药物（BDZ）是治疗焦虑症最常用的首选药物，但其存在诸如镇静、肌肉紊乱、成瘾性以及与酒精和中枢神经系统抑制药物的协同作用等副作用。目前，药理学研究致力于寻找与苯二氮䓬类药物疗效相当但无副作用的抗焦虑药物。本综述报告了治疗焦虑症新药的药物研发状况。对N5C“Pharmaprojects”搜索（抗焦虑类）所选项目的仔细分析得出以下分类：A）与GABA - A受体复合物相互作用的药物，包括类苯二氮䓬类药物、部分苯二氮䓬激动剂（β - 咔啉）以及通过尚未明确的机制与GABA - A复合物相互作用的药物（15种化合物）；B）作为CCK - B拮抗剂的药物（5种化合物）；C）与5 - 羟色胺能功能相互作用的药物（30种化合物），细分为：（i）5 - HT1A受体激动剂，（ii）5 - HT2受体拮抗剂，以及（iii）5 - HT3受体拮抗剂；D）具有其他机制的药物（22种化合物）。基于这些结果，无法确定正在研发的所选药物发挥抗焦虑作用的共同机制。因此，不同的生物学机制似乎在不同的焦虑症中发挥着特定作用。
