Document Detail

Partial and full agonists/inverse agonists affect [35S]TBPS binding at different occupancies of central benzodiazepine receptors.
MedLine Citation:
PMID:  8223948     Owner:  NLM     Status:  MEDLINE    
Concentration-dependent effects of benzodiazepine receptor ligands were examined on nonequilibrium binding of t-butylbicyclophosphoro[35S]thionate (TBPS, 20 min of incubation at 25 degrees C) to synaptosomal membranes of rat cerebral cortex. Benzodiazepine receptor occupancies were calculated from the displacing potencies of the ligands determined for [3H]flumazenil binding under identical conditions. Greater maximal enhancing (i.e. accelerating) effects of the full agonists diazepam and flunitrazepam on [35S]TBPS binding were reached at lower occupancies of benzodiazepine receptors than the smaller enhancing effects of the partial agonists bretazenil and the beta-carboline ZK 91296. Similarly, the maximal decreasing effect of the full inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) on TBPS binding was reached at lower occupancy than that of the partial inverse agonist FG 7142. Half-maximal effects on TBPS binding corresponded to about 20-30% occupancies for the full agonists and DMCM, while for partial agonists and FG 7142 they exceeded 60-80% occupancies. Different (concave versus convex) shapes of the occupancy-effect curves can also differentiate partial from full agonists and inverse agonists. The results suggest that different pharmacological efficacies of benzodiazepine receptor ligands are associated with differences in coupling between benzodiazepine and convulsant binding sites to modulate the chloride ionophores.
G Maksay
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  246     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1993 Aug 
Date Detail:
Created Date:  1993-12-17     Completed Date:  1993-12-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  255-60     Citation Subset:  IM    
Department of Molecular Pharmacology, Hungarian Academy of Sciences, Budapest.
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MeSH Terms
Bicyclo Compounds / metabolism*
Bicyclo Compounds, Heterocyclic*
Cerebral Cortex / drug effects*,  metabolism
Chlorides / metabolism*
Convulsants / metabolism*
Ionophores / metabolism*
Radioligand Assay
Receptors, GABA-A / drug effects*,  metabolism
Sulfur Radioisotopes / diagnostic use
Reg. No./Substance:
0/Bicyclo Compounds; 0/Bicyclo Compounds, Heterocyclic; 0/Chlorides; 0/Convulsants; 0/Ionophores; 0/Receptors, GABA-A; 0/Sulfur Radioisotopes; 70636-86-1/tert-butylbicyclophosphorothionate

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