Neurochemical profile of Lu 19-005, a potent inhibitor of uptake of dopamine, noradrenaline, and serotonin

J Neurochem. 1985 May;44(5):1615-22. doi: 10.1111/j.1471-4159.1985.tb08803.x.

Abstract

The neurochemical profile of a new compound, Lu 19-005 [(+/-)trans-3-(3,4-dichlorophenyl)-N-methyl-1-indanamine hydrochloride], has been investigated. Lu 19-005 is a potent inhibitor of the synaptosomal uptake of 3,4-dihydroxyphenylethylamine (dopamine, DA), noradrenaline (NA), and 5-hydroxytryptamine (5-HT, serotonin). In this respect it resembles diclofensine, whereas compounds such as GBR 13.069 and bupropion are more selective DA-uptake inhibitors. Although Lu 19-005 releases DA in in higher concentrations it must be considered as an uptake inhibitor, as the accumulation of DA is inhibited in much lower concentrations. Lu 19-005 attenuates the DA and NA depletion caused by 6-hydroxydopamine in mouse brain. These properties confirm the DA- and NA-uptake-inhibitory properties of the compound. In receptor-binding models and functional in vitro tests Lu 19-005 is devoid of dopaminergic-, serotonergic-, noradrenergic-, histaminergic-, and cholinergic-inhibiting properties. Since DA, NA, and 5-HT seem to be involved in depression, the profile of Lu 19-005--with equally potent activity on the three neuronal systems--makes it an interesting experimental tool and a potential new antidepressant agent.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Biological Transport / drug effects
  • Brain / metabolism*
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Female
  • Guinea Pigs
  • Indans / pharmacology*
  • Indenes / pharmacology*
  • Kinetics
  • Male
  • Mice
  • Norepinephrine / metabolism*
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Receptors, Neurotransmitter / drug effects
  • Serotonin / metabolism*
  • Synaptosomes / metabolism

Substances

  • Antidepressive Agents
  • Indans
  • Indenes
  • Receptors, Neurotransmitter
  • Serotonin
  • Lu 19005
  • Dopamine
  • Norepinephrine