Neurochemical profile of Lu 19-005, a potent inhibitor of uptake of dopamine, noradrenaline, and serotonin.
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.
Hyttel
J
J
Larsen
J J
JJ
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D007189:Indans / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D000928:Antidepressive Agents; D007189:Indans; D007192:Indenes; D017981:Receptors, Neurotransmitter; D012701:Serotonin; C045117:Lu 19005; D004298:Dopamine; D009638:Norepinephrine