caa a22 4500 469120592 CHVBK 20180323133137.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF02245136 doi (NATIONALLICENCE)springer-10.1007/BF02245136 Stereoselective behavioral effects of Lu 19-005 in monkeys: relation to binding at cocaine recognition sites [Elektronische Daten] [S. Rosenzweig-Lipson, Jack Bergman, R. Spealman, B. Madras] 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)methoxyl]ethyl}-4-(3-phenylpropyl)piperazin e) 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. At 37° C, Lu 20-043 was approximately 36 times more potent than Lu 20-043 in inhibiting the binding of [3H]CFT, whereas at 0-4° C, the difference in potency was only about 2-fold. The increased stereoselectivity at 37° C was due to a reduced potency for Lu 20-043. The results support the view that the behavioral effects of Lu 19-005 and its enantiomers are mediated at cocaine recognition sites associated with the dopamine uptake system. The results also show that incubation temperature can be a relevant factor in determining the relative potencies of drugs at [3H]CFT binding sites in vitro. Springer-Verlag, 1992 Lu 19-005 nationallicence Stereoselectivity nationallicence Monoamine uptake inhibitor nationallicence Cocaine nationallicence GBR 12909 nationallicence Cocaine recognition site nationallicence Operant behavior nationallicence Radioreceptor assay nationallicence Temperature dependence nationallicence Indatraline nationallicence Rosenzweig-Lipson S. Harvard Medical School, New England Regional Primate Research Center, 01772-9102, Southborough, MA, USA aut Bergman Jack Harvard Medical School, New England Regional Primate Research Center, 01772-9102, Southborough, MA, USA aut Spealman R. Harvard Medical School, New England Regional Primate Research Center, 01772-9102, Southborough, MA, USA aut Madras B. Harvard Medical School, New England Regional Primate Research Center, 01772-9102, Southborough, MA, USA aut Psychopharmacology Springer-Verlag 107/2-3(1992-06-01), 186-194 0033-3158 107:2-3<186 1992 107 213 https://doi.org/10.1007/BF02245136 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245136 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rosenzweig-Lipson S. Harvard Medical School, New England Regional Primate Research Center, 01772-9102, Southborough, MA, USA aut NATIONALLICENCE 700 1- Bergman Jack Harvard Medical School, New England Regional Primate Research Center, 01772-9102, Southborough, MA, USA aut NATIONALLICENCE 700 1- Spealman R. Harvard Medical School, New England Regional Primate Research Center, 01772-9102, Southborough, MA, USA aut NATIONALLICENCE 700 1- Madras B. Harvard Medical School, New England Regional Primate Research Center, 01772-9102, Southborough, MA, USA aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 107/2-3(1992-06-01), 186-194 0033-3158 107:2-3<186 1992 107 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer