title: Effect of 7-(3-[4-(2,3-dimethylphenyl)piperazinyl]propoxy)- 2(1H)-quinolinone (OPC-4392), a newly synthesized agonist for presynaptic dopamine D2 receptor, on tyrosine hydroxylation in rat striatal slices.
abstract: The effects of a newly synthesized compound, 7-(3-[4-(2,3-dimethylphenyl)piperazinyl]propoxy)-2(1H)-quinolinone (OPC-4392), on tyrosine hydroxylation in situ and in vitro were studied using rat striatal slices and tyrosine hydroxylase (TH) purified from bovine adrenal medulla, respectively. OPC-4392 dose-dependently inhibited L-dihydroxyphenylalanine (DOPA) formation in rat striatal slices with IC50 values of about 10(-6) M. The inhibitory effect of OPC-4392 on in situ DOPA formation was dose-dependently reversed by addition of sulpiride, a dopamine D2 receptor antagonist, whereas no change was observed by addition of nomifensine (5 X 10(-6) M), a blocker of dopamine uptake. From in vitro experiment using purified TH, OPC-4392 affected neither the enzymatic activity nor the Km value for 6-methyl-5,6,7,8-tetrahydropterin (6MPH4). These results suggest that OPC-4392 impairs in situ DOPA formation by stimulating presynaptic dopamine D2 receptor as a dopamine agonist, and not by directly inhibiting the TH activity.
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000302:isolation & purification / Q000494:pharmacology*; D011804:Quinolines / Q000302:isolation & purification / Q000494:pharmacology*; D015363:Quinolones; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D010879:Piperazines; D011804:Quinolines; D015363:Quinolones; D011954:Receptors, Dopamine; D017981:Receptors, Neurotransmitter; C054574:OPC 4392; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase