Barbiturate shift as a tool for determination of efficacy of benzodiazepine-receptor ligands |
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Authors: | T Honoré M Nielsen C Braestrup |
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Institution: | 1. A/S Ferrosan, Research Division, Sydmarken 5, DK-2860 Soeborg, Denmark;2. Sct. Hans Hospital, DK-4000 Roskilde, Denmark |
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Abstract: | 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. |
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Keywords: | Barbiturate shift Benzodiazepine-receptor ligands Efficacy BZ agonist BZ antagonist BZ inverse agonist |
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