Sieghart W, Schuster A
Biochem Pharmacol. 1984 Dec 15;33(24):4033-8. doi: 10.1016/0006-2952(84)90017-0.
The structure-affinity relationship of benzodiazepine receptor ligands for binding to their receptors was investigated by measuring the potency of 41 benzodiazepines or benzodiazepine analogues and of 9 non-benzodiazepines for inhibition of [3H]flunitrazepam binding to cerebellar or hippocampal membranes. It was found that a chloro or a fluoro substitutent in position 2' enhanced whereas substituents in position 3 and substituents larger than a methyl group in position 1 of the benzodiazepine ring system reduced the potency of benzodiazepines for inhibition of [3H]flunitrazepam binding in cerebellum or hippocampus. In addition, several benzodiazepines could be identified which have a higher affinity for benzodiazepine receptors in cerebellum than for those in hippocampus. A selectivity of benzodiazepines for their receptors in cerebellum seems to be caused not only by certain substituents in position 1 but also by a chloro group in position 2' and together with this substituent by a hydroxy group in position 3.
通过测定41种苯二氮䓬类药物或苯二氮䓬类似物以及9种非苯二氮䓬类药物对[³H]氟硝西泮与小脑或海马体膜结合的抑制效力，研究了苯二氮䓬受体配体与其受体结合的构效关系。结果发现，苯二氮䓬环系统2'位的氯或氟取代基增强了其效力，而3位的取代基以及苯二氮䓬环1位大于甲基的取代基则降低了苯二氮䓬类药物对小脑或海马体中[³H]氟硝西泮结合的抑制效力。此外，还鉴定出几种对小脑苯二氮䓬受体的亲和力高于海马体中受体的苯二氮䓬类药物。苯二氮䓬类药物对小脑受体的选择性似乎不仅由1位的某些取代基引起，还由2'位的氯取代基以及与该取代基一起的3位羟基引起。
