| Stereoselective behavioral effects of Lu 19-005 in monkeys: relation to binding at cocaine recognition sites. | |
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MedLine Citation:
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PMID: 1377395 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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) |
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Authors:
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S Rosenzweig-Lipson; J Bergman; R D Spealman; B K Madras |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Psychopharmacology Volume: 107 ISSN: 0033-3158 ISO Abbreviation: Psychopharmacology (Berl.) Publication Date: 1992 |
Date Detail:
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Created Date: 1992-07-30 Completed Date: 1992-07-30 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7608025 Medline TA: Psychopharmacology (Berl) Country: GERMANY |
Other Details:
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Languages: eng Pagination: 186-94 Citation Subset: IM |
Affiliation:
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Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772-9102. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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DA00499/DA/NIDA NIH HHS; DA03774/DA/NIDA NIH HHS; DA06303/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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