Distinction of benzodiazepine agonists from antagonists by photoaffinity labelling of benzodiazepine receptors in vitro.
When membranes of rat cerebellum are exposed to UV light in the presence of flunitrazepam this ligand can be incorporated into one of the assumed 4 benzodiazepine binding sites of the GABA-benzodiazepine receptor complex. This irreversible incorporation of flunitrazepam, in contrast to reversible binding of this substance, leads to conformational changes of the remaining 3 benzodiazepine binding sites which result in a decreased affinity of benzodiazepine agonists, but not of benzodiazepine antagonists. The investigation of the affinity of drugs for [3H]benzodiazepine antagonist binding before and after photoaffinity labelling of benzodiazepine receptors with flunitrazepam can therefore be used as a sensitive and simple test to distinguish between agonists and antagonists in vitro.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001667:Binding, Competitive; D002243:Carbolines / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D005445:Flunitrazepam / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A; D014466:Ultraviolet Rays
D014151:Anti-Anxiety Agents; D002243:Carbolines; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; D011963:Receptors, GABA-A; C026072:1-methyl-beta-carboline-3-carboxylic acid; D005445:Flunitrazepam