Coenen A M, van Luijtelaar E L
Department of Psychology, University of Nijmegen, The Netherlands.
Pharmacol Biochem Behav. 1989 Jan;32(1):27-35. doi: 10.1016/0091-3057(89)90206-2.
In the present series of experiments, effects of a full benzodiazepine receptor agonist (diazepam) are described and compared with those of a partial benzodiazepine receptor agonist (ZK 91296) and an inverse partial benzodiazepine receptor agonist (FG 7142), both compounds of the beta-carboline family. In a rat model for generalized absence epilepsy, the anticonvulsant, the hypnotic and the myorelaxant properties were investigated, as well as effects on on-going behavior and effects on the electroencephalogram (EEG). While diazepam showed all behavioral and electrophysiological changes characteristic for the benzodiazepines, the partial agonist ZK 91296 reduced seizure activity without inducing any signs of sedation, sleepiness, myorelaxation and changes in behavior or EEG spectral content. The partial inverse agonist FG 7142 aggrevated epileptic activity, with slightly enhanced immobile behavior, suggesting some anxiogenic properties. The results not only demonstrate that the multiple effects of the benzodiazepines could be separated by these compounds, but also that the anticonvulsant activity is not related to changes in spectral content of the EEG. Because of its selective activity, ZK 91296 appears to be more suitable than diazepam in reducing seizure activity. Finally, FG 7142 seems a genuine partial inverse agonist which has some, but not all, of the inverse effects of a full agonist.
在本系列实验中，描述了一种完全苯二氮䓬受体激动剂（地西泮）的作用，并将其与一种部分苯二氮䓬受体激动剂（ZK 91296）和一种反向部分苯二氮䓬受体激动剂（FG 7142）的作用进行了比较，这两种化合物均属于β-咔啉家族。在一种全身性失神癫痫大鼠模型中，研究了其抗惊厥、催眠和肌松特性，以及对持续行为的影响和对脑电图（EEG）的影响。虽然地西泮表现出苯二氮䓬类药物所有典型的行为和电生理变化，但部分激动剂ZK 91296降低了癫痫活动，且未诱发任何镇静、嗜睡、肌松以及行为或EEG频谱成分变化的迹象。部分反向激动剂FG 7142加剧了癫痫活动，同时轻微增强了不动行为，提示具有一定的致焦虑特性。结果不仅表明这些化合物可以区分苯二氮䓬类药物的多种作用，还表明抗惊厥活性与EEG频谱成分的变化无关。由于其选择性活性，ZK 91296在降低癫痫活动方面似乎比地西泮更合适。最后，FG 7142似乎是一种真正的部分反向激动剂，具有完全激动剂的一些但并非全部反向作用。
