File S E, Pellow S
Br J Pharmacol. 1985 Nov;86(3):729-35. doi: 10.1111/j.1476-5381.1985.tb08952.x.
In addition to possessing anti-anxiety activity in man, triazolobenzodiazepines have been reported to have antidepressant and antipanic properties. In this they differ from classical 1,4-benzodiazepines that have only anti-anxiety activity. The purpose of the present study was to examine the effects of the triazolobenzodiazepines in two animal tests of anxiety and in the holeboard, to see whether clear differences could be observed between them and the 1,4-benzodiazepines. After acute administration, U-43,465 (16 mg kg-1) had a significant anxiolytic effect in the social interaction test. Neither adinazolam (1-3.5 mg kg-1) nor alprazolam (0.125-2 mg kg-1) had a significant effect. It is suggested that this is because, with adinazolam and alprazolam, doses at which anxiolytic effects can be observed are close to those at which sedative effects can be observed. U-43,465 (8-16 mg kg-1) and alprazolam (1-2 mg kg-1) had significant anxiolytic effects in the elevated plus-maze test of anxiety. U-43,465 (8-32 mg kg-1), adinazolam (0.5-5 mg kg-1) and alprazolam (0.2-2.0 mg kg-1) caused dose-related reductions in exploratory head-dipping, locomotor activity and rearing in the holeboard. In general the results seen in the three tests with the triazolobenzodiazepines alprazolam and adinazolam were similar to those seen with classical 1,4-benzodiazepines. With U-43,465, however, an anxiolytic effect was observed in the social interaction test after acute treatment; chronic treatment is required to see an effect with classical 1,4-benzodiazepines. In this U-43,465 resembles the effects of several novel non-benzodiazepine putative anxiolytic compounds that are believed to have less sedative potential than the benzodiazepines.
除了在人体中具有抗焦虑活性外，三唑并苯二氮䓬类药物还被报道具有抗抑郁和抗惊恐特性。在这方面，它们不同于仅具有抗焦虑活性的经典1,4 - 苯二氮䓬类药物。本研究的目的是在两项动物焦虑试验和洞板试验中检验三唑并苯二氮䓬类药物的效果，以观察它们与1,4 - 苯二氮䓬类药物之间是否能观察到明显差异。急性给药后，U - 43,465（16毫克/千克）在社交互动试验中具有显著的抗焦虑作用。阿地唑仑（1 - 3.5毫克/千克）和阿普唑仑（0.125 - 2毫克/千克）均无显著作用。据推测，这是因为对于阿地唑仑和阿普唑仑，能观察到抗焦虑作用的剂量接近能观察到镇静作用的剂量。U - 43,465（8 - 16毫克/千克）和阿普唑仑（1 - 2毫克/千克）在高架十字迷宫焦虑试验中具有显著的抗焦虑作用。U - 43,465（8 - 32毫克/千克）、阿地唑仑（0.5 - 5毫克/千克）和阿普唑仑（0.2 - 2.0毫克/千克）使洞板试验中的探索性探头次数、运动活性和竖毛行为出现剂量相关的减少。总体而言，在三项试验中观察到的三唑并苯二氮䓬类药物阿普唑仑和阿地唑仑的结果与经典1,4 - 苯二氮䓬类药物的结果相似。然而，对于U - 43,465，急性治疗后在社交互动试验中观察到了抗焦虑作用；而经典1,4 - 苯二氮䓬类药物则需要慢性治疗才能看到效果。在这方面，U - 43,465类似于几种新型非苯二氮䓬类假定抗焦虑化合物的作用，这些化合物被认为比苯二氮䓬类药物具有更低的镇静潜力。
