Document Detail


Stereoselective behavioral effects of Lu 19-005 in monkeys: relation to binding at cocaine recognition sites.
MedLine Citation:
PMID:  1377395     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of the monoamine uptake inhibitor Lu 19-005 ((+/-)-trans-3-(3,4-dichlorophenyl)-N-methyl-1-indanamine) and its (+) and (-) enantiomers, Lu 20-042 and Lu 20-043, were compared with those of cocaine and the selective dopamine uptake inhibitor GBR 12909 (1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine) in behavioral and radioligand binding experiments. Behavioral experiments were conducted in groups of squirrel monkeys trained under fixed-interval schedules of reinforcement in which responding was maintained either by presentation of food or by termination of a visual stimulus associated with mild electric shock. Radioligand binding studies were conducted using [3H]CFT and [3H]GBR 12935 to label elements of the dopamine uptake system in caudate-putamen membranes of cynomolgus monkeys. All drugs produced dose-related increases in response rate under the fixed-interval schedules. Lu 19-005, Lu 20-042, and Lu 20-043 had relatively slow onsets (approximately 2 h) and relatively long durations of action, with effects persisting for two or more days following administration. Stereoselectivity was evident in the behavioral effects of the enantiomers of Lu 19-005, with Lu 20-042 being approximately 14 times more potent than Lu 20-043. In radioligand binding experiments, Lu 19-005 and its enantiomers were potent inhibitors of specifically bound [3H]CFT and [3H]GBR 12935. As in behavioral experiments, Lu 20-042 was more potent than Lu 20-043. The degree of stereoselectivity, however, varied with the temperature of the assay medium.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
S Rosenzweig-Lipson; J Bergman; R D Spealman; B K Madras
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Psychopharmacology     Volume:  107     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  1992  
Date Detail:
Created Date:  1992-07-30     Completed Date:  1992-07-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  186-94     Citation Subset:  IM    
Affiliation:
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772-9102.
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MeSH Terms
Descriptor/Qualifier:
Animals
Behavior, Animal / drug effects*
Binding, Competitive / drug effects
Carrier Proteins*
Cocaine / pharmacology
Conditioning, Operant / drug effects
Dopamine / metabolism*
Indans / pharmacology*
Ligands
Male
Piperazines / pharmacology
Receptors, Drug / drug effects,  metabolism*
Reinforcement Schedule
Saimiri
Stereoisomerism
Grant Support
ID/Acronym/Agency:
DA00499/DA/NIDA NIH HHS; DA03774/DA/NIDA NIH HHS; DA06303/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Indans; 0/Ligands; 0/Piperazines; 0/Receptors, Drug; 0/cocaine receptor; 50-36-2/Cocaine; 67469-78-7/vanoxerine; 97229-15-7/Lu 19005

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


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