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

Life Sci. 1988;42(3):343-9. doi: 10.1016/0024-3205(88)90644-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / drug effects
  • Corpus Striatum / enzymology*
  • Dihydroxyphenylalanine / metabolism
  • Dose-Response Relationship, Drug
  • Hydroxylation
  • In Vitro Techniques
  • Male
  • Piperazines / isolation & purification
  • Piperazines / pharmacology*
  • Quinolines / isolation & purification
  • Quinolines / pharmacology*
  • Quinolones*
  • Rats
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / metabolism
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / metabolism
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • Piperazines
  • Quinolines
  • Quinolones
  • Receptors, Dopamine
  • Receptors, Neurotransmitter
  • OPC 4392
  • Dihydroxyphenylalanine
  • Tyrosine 3-Monooxygenase