Hsieh M T
Int J Clin Pharmacol Ther Toxicol. 1982 May;20(5):227-35.
The effects of 1,5-benzodiazepine clobazam and diazepam were evaluated with regard to behavioral locomotor changes in rats. A concurrent focus of investigation was whether or not both benzodiazepines interact with central monoaminergic and GABAergic mechanisms. Diazepam was more active than clobazam in reducing locomotor activity. The stimulation of locomotor activity induced by L-dopa plus benserazide, and methamphetamine was significantly counteracted by diazepam but unaffected by clobazam. Hypomotility produced by alpha-methyl-p-tyrosine was markedly augmented with both drugs. Locomotor suppression elicited by 5-HTP, activating central serotoninergic transmission, was more potently reversed by clobazam than by diazepam. In addition, arousal behavior produced by p-CPA, inactivating central serotoninergic transmission, was completely abolished by both drugs. Furthermore, in combination with AOAA, known to inhibit motor activity, diazepam had a synergistic effect, and picrotoxin-produced suppression was significantly antagonized by diazepam. Both benzodiazepines thus may exert their behavioral depressant effects by reducing catecholaminergic and serotoninergic activity, and also by promoting GABA-mediated inhibition in the central nervous system. Clobazam is more effective than diazepam in reducing serotoninergic activity, but less effective in reducing catecholaminergic activity and increasing GABAergic activity.
研究了1,5-苯二氮䓬类药物氯巴占和地西泮对大鼠行为性运动变化的影响。同时研究的一个重点是这两种苯二氮䓬类药物是否与中枢单胺能和GABA能机制相互作用。地西泮在降低运动活性方面比氯巴占更有效。左旋多巴加苄丝肼和甲基苯丙胺诱导的运动活性刺激被地西泮显著抵消，但不受氯巴占影响。α-甲基对酪氨酸产生的运动减退在两种药物作用下均明显增强。5-羟色氨酸激活中枢5-羟色胺能传递引起的运动抑制，氯巴占比地西泮更有效地逆转。此外，对氯苯丙氨酸使中枢5-羟色胺能传递失活产生的觉醒行为，两种药物均能完全消除。此外，与已知抑制运动活性的氨基氧乙酸联合使用时，地西泮有协同作用，印防己毒素产生的抑制作用被地西泮显著拮抗。因此，两种苯二氮䓬类药物可能通过降低儿茶酚胺能和5-羟色胺能活性，以及通过促进中枢神经系统中GABA介导的抑制作用来发挥其行为抑制作用。氯巴占在降低5-羟色胺能活性方面比地西泮更有效，但在降低儿茶酚胺能活性和增加GABA能活性方面效果较差。
