Presynaptic inhibition of excitatory input from the substantia nigra to caudate nucleus neurons by a substituted quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl)piperazinyl)propoxy]-2(1H)-quinolinone (OPC-4392).
The effects of a newly synthesized quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl)piperazinyl) propoxy]-2(1H)-quinolinone (OPC-4392) on neuronal activities of the caudate nucleus (CN) were investigated in cats anesthetized with alpha-chloralose using a microiontophoretic method. In the CN neurons of which spikes elicited by stimulation of the pars compacta of substantia nigra (SN) were suppressed by iontophoretically applied domperidone, a dopamine D-2 receptor antagonist, application of OPC-4392 (100-200 nA) inhibited the spike generation induced by SN stimulation. Conversely, the CN neurons insensitive to domperidone were unaffected by OPC-4392. Iontophoretic application of CPC-4392 up to 200 nA did not affect glutamate-induced firing of the CN neurons, of which the firing was blocked by dopamine less than 100 nA. In addition, OPC-4392 did not inhibit firing induced by bromocriptine, a dopamine D-2 agonist; while domperidone suppressed the bromocriptine-induced firing without affecting the glutamate-induced firing. These results suggest that OPC-4392 acts on the dopaminergic nerve terminals and inhibits excitatory transmission from the SN to the CN.
Sasa
M
M
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Ohno
Y
Y
Takaori
S
S
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002415:Cats; D002421:Caudate Nucleus / Q000187:drug effects*; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D009434:Neural Pathways / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D015363:Quinolones; D012970:Sodium Glutamate / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects*
D010879:Piperazines; D011804:Quinolines; D015363:Quinolones; C054574:OPC 4392; D001971:Bromocriptine; D004294:Domperidone; D004298:Dopamine; D012970:Sodium Glutamate