Barbiturate shift as a tool for determination of efficacy of benzodiazepine-receptor ligands.
The change in benzodiazepine(BZ)-receptor affinity for selected BZ receptor ligands, induced by pentobarbital at 30 degrees C in the presence of 200 mM NaCl (barbiturate shift) was investigated. The affinity for benzodiazepines (e.g. flunitrazepam) was increased approximately two-fold by the presence of pentobarbital (1 mM) whereas the affinity for convulsive BZ-receptor ligands (e.g. DMCM ) was reduced approximately two-fold. The affinity for BZ-receptor antagonists (e.g. Ro 15-1788) was unaltered by pentobarbital. The results obtained suggest that barbiturate shifts have predictive value in determining the pharmacological efficacies of BZ-receptor ligands. However, compounds such as CL 218.872 and ZK 93423 would not have been recognized as agonists, notwithstanding their clear agonistic profile in pharmacological tests.
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002243:Carbolines / Q000378:metabolism; D003292:Convulsants / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism*; D066298:In Vitro Techniques; D007476:Ionophores / Q000378:metabolism; D008024:Ligands; D010424:Pentobarbital / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A; D012965:Sodium Chloride / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism*
D002243:Carbolines; D003292:Convulsants; D007476:Ionophores; D008024:Ligands; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D012965:Sodium Chloride; D005445:Flunitrazepam; D010424:Pentobarbital