Affinity of various ligands for benzodiazepine receptors in rat cerebellum and hippocampus.
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.
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D005445:Flunitrazepam / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008024:Ligands; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014316:Tritium
D008024:Ligands; D011963:Receptors, GABA-A; D014316:Tritium; D001569:Benzodiazepines; D005445:Flunitrazepam