In vivo neurochemical profile of dopamine uptake inhibitors and releasers in rat caudate-putamen.
The in vivo neurochemical profile of recently synthesized dopamine (DA) uptake inhibitors (Lu 19-005, Lu 17-133 and GBR 12.921) is described. The antidepressant, nomifensine, as well as another typical DA uptake inhibitor, methylphenidate, was also tested with the microdialysis technique. Most of the new DA uptake inhibitors induced a gradual dose- and time-dependent accumulation of extracellular DA with a weak influence on DA metabolites, similar to that of methylphenidate. Nomifensine, however, caused a DA overflow during the first hour after injection. This was distinguishable from the effect of other uptake inhibitors but comparable to amphetamine. The moderate increase of DOPAC induced by nomifensine compared to the marked decrease produced by amphetamine corroborates reports that the DA 'release' induced by these drugs is mediated by different mechanisms, originating from different intracellular storage pools of DA. The fact that nomifensine can be distinguished from other uptake inhibitors shows clearly that evaluation of dynamic changes in transmitter overflow provides information pertinent to the overall neurochemical characterization of a drug.
Hurd
Y L
YL
Karolinska Institute, Department of Pharmacology, Stockholm, Sweden.
Ungerstedt
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D007189:Indans / Q000494:pharmacology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009627:Nomifensine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D015259:Dopamine Agents; D007189:Indans; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D008774:Methylphenidate; C039737:1-(2-(diphenylmethoxy)ethyl)-4-(3-phenyl-2-propenyl)piperazine; C061234:(3-(3,4-dichlorophenyl)indan-1-yl)-4-methylpiperazine; C045117:Lu 19005; D004298:Dopamine; D006719:Homovanillic Acid