Characterization of [3H]quinpirole binding to D2-like dopamine receptors in rat brain

J Pharmacol Exp Ther. 1992 Sep;262(3):929-35.


The putative D2 dopamine receptor agonist quinpirole (LY 171,555) is the most widely used D2 agonist in in vivo and in vitro studies of D2 receptor-mediated effects. In addition, quinpirole may have even higher affinity for the recently described D3 dopamine receptor. The present study describes the in vitro binding properties of newly developed [3H]quinpirole in rat brain. [3H]Quinpirole binding was characterized in striatal membrane homogenate preparations using a filtration assay. Nonspecific binding was defined by 1 microM (+)-butaclamol. Specific [3H]quinpirole binding was saturable, and dependent on temperature, membrane concentration, sodium concentration and guanine nucleotides. Saturation analysis revealed high affinity binding characteristics (KD = 2.3 +/- 0.3 nM) which were confirmed by association-dissociation kinetics. The pharmacological profile of [3H]quinpirole binding in striatum was: (-)-N-n-propylnorapomorphine (+/-)-2-amino-6,7-dihydroxyl-1,2,3,4-tetrahydronaphthalene greater than or equal to quinpirole greater than apomorphine greater than bromocriptine greater than dopamine greater than SKF 38393 much greater than 5-hydroxytryptamine for putative dopamine agonists; spiperone greater than (+)-butaclamol greater than haloperidol greater than (-)-sulpiride greater than clozapine greater than SCH 23390 much greater than cinanserin for antagonists. [3H]Quinpirole binding exhibited stereoselectivity: (-)-sulpiride greater than (+)-sulpiride and (+)-butaclamol greater than (-)-butaclamol. This pharmacological profile is similar, though-not identical, to that observed for [3H] spiperone-labeled D2 receptors. The regional distribution of [3H]quinpirole binding sites roughly paralleled the distribution of [3H]spiperone binding sites, with greatest densities present in the striatum, nucleus accumbens and olfactory tubercles.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Brain / metabolism*
  • Culture Techniques
  • Dopamine Agents / metabolism*
  • Dopamine Antagonists
  • Ergolines / metabolism*
  • Male
  • Quinpirole
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Spiperone / metabolism


  • Dopamine Agents
  • Dopamine Antagonists
  • Drd3 protein, rat
  • Ergolines
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Quinpirole
  • Spiperone