Pramipexole, a dopamine D2 autoreceptor agonist, decreases the extracellular concentration of dopamine in vivo

Eur J Pharmacol. 1991 Jul 23;200(1):65-72. doi: 10.1016/0014-2999(91)90666-e.

Abstract

Pramipexole (SND 919) is a dopamine D2 autoreceptor agonist which is structurally related to talipexole (B-HT 920), a potential antipsychotic agent. The aim of this study was to investigate the effects of pramipexole on the extracellular concentration of dopamine in vivo. Dopamine and its metabolites, 3,4-dihydrophenylacetic acid and homovanillic acid, were measured in the anterior striatum of freely moving rats by microdialysis and high-performance liquid chromatography with electrochemical detection. Pramipexole (30 and 100 micrograms/kg) caused long-lasting decreases in the extracellular concentrations of dopamine and its metabolites. Talipexole (30 micrograms/kg) produced similar effects. Sulpiride (5 mg/kg), a selective dopamine D2 antagonist, caused a transient increase in the concentration of dopamine and long-lasting increases in the concentrations of its metabolites; it also reversed the effects of pramipexole. SCH-23390 (100 micrograms/kg), a selective dopamine D1 receptor antagonist, caused a transient increase in the concentration of dopamine but did not affect the concentrations of the metabolites. SCH-23390 failed to reverse the effects of pramipexole. These results indicate that pramipexole reduces the extracellular concentrations of dopamine and its metabolites in vivo through a reversible interaction with the dopamine D2 receptor.

Publication types

  • Comparative Study

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Analysis of Variance
  • Animals
  • Azepines / pharmacology
  • Benzothiazoles
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dialysis
  • Dopamine / metabolism*
  • Dopamine Agents / pharmacology*
  • Dopamine Antagonists
  • Extracellular Space / metabolism
  • Homovanillic Acid / metabolism
  • Male
  • Pramipexole
  • Rats
  • Rats, Inbred Strains
  • Sulpiride / pharmacology
  • Thiazoles / pharmacology*

Substances

  • Azepines
  • Benzothiazoles
  • Dopamine Agents
  • Dopamine Antagonists
  • Thiazoles
  • 3,4-Dihydroxyphenylacetic Acid
  • talipexole
  • Sulpiride
  • Pramipexole
  • Dopamine
  • Homovanillic Acid