Document Detail


Interaction of abecarnil, bretazenil, and RO 19-8022 with diazepam-sensitive and -insensitive benzodiazepine sites in the rat cerebellum and cerebral cortex.
MedLine Citation:
PMID:  7475974     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Abecarnil, bretazenil, and Ro 19-8022 inhibited the binding of [3H]Ro 15-4513 to diazepamsensitive and -insensitive sites in the rat cerebellum and cerebral cortex, but all three had a much higher affinity for the diazepam-sensitive sites in both tissues. The GABA-shift for bretazenil and Ro 19-8022 was low ( < 2) for all sites studied, consistent with their partial agonistic profile. The GABA-shift for abecarnil was appreciably higher for diazepam-sensitive binding in the cerebellum than in the cerebral cortex (1.97 vs 1.18). Furthermore, the GABA-shift for abecarnil was markedly different for the diazepam-sensitive and -insensitive sites in the cerebellum (1.97 vs 0.71). All three compounds inhibited [3H]Ro 15-4513 binding to the diazepam-sensitive sites with a slope factor > 1, suggestive of positive cooperativity in their binding to GABAA receptors. Abecarnil only partially inhibited diazepam-insensitive binding of [3H]Ro 15-4513 in the cerebellum, indicating that this site can be differentiated into abecarnil-sensitive and -insensitive components.
Authors:
A K Mehta; R P Shank
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Life sciences     Volume:  57     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  1995  
Date Detail:
Created Date:  1995-12-21     Completed Date:  1995-12-21     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2215-22     Citation Subset:  IM    
Affiliation:
R.W. Johnson Pharmaceutical Research Institute, Spring House PA 19477-0776, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Anxiety Agents / pharmacology
Benzodiazepinones / pharmacology*
Binding Sites
Brain / drug effects,  metabolism*
Carbolines / pharmacology*
Cell Membrane / drug effects,  metabolism
Cerebellum / drug effects,  metabolism
Cerebral Cortex / drug effects,  metabolism
Diazepam / pharmacology*
Male
Pyrrolidines / pharmacology*
Quinolizines / pharmacology*
Rats
Rats, Wistar
Receptors, GABA-A / drug effects*,  metabolism
Chemical
Reg. No./Substance:
0/Anti-Anxiety Agents; 0/Benzodiazepinones; 0/Carbolines; 0/Pyrrolidines; 0/Quinolizines; 0/Receptors, GABA-A; 104604-66-2/Ro 19-8022; 111841-85-1/abecarnil; 439-14-5/Diazepam; 84379-13-5/bretazenil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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