Stereoselective behavioral effects of Lu 19-005 in monkeys: relation to binding at cocaine recognition sites

Psychopharmacology (Berl). 1992;107(2-3):186-94. doi: 10.1007/BF02245136.

Abstract

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)

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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
  • Receptors, Drug / metabolism*
  • Reinforcement Schedule
  • Saimiri
  • Stereoisomerism

Substances

  • Carrier Proteins
  • Indans
  • Ligands
  • Piperazines
  • Receptors, Drug
  • cocaine receptor
  • vanoxerine
  • Lu 19005
  • Cocaine
  • Dopamine