Functional potencies of new antiparkinsonian drugs at recombinant human dopamine D1, D2 and D3 receptors

Eur J Pharmacol. 1999 Feb 5;366(2-3):293-300. doi: 10.1016/s0014-2999(98)00896-6.


We measured the affinities of bromocriptine, pramipexole, pergolide and ropinirole at human recombinant dopamine D1, D2 and D3 receptors in binding and functional tests. All four compounds bound with high affinity at the dopamine D3 receptor; bromocriptine and pergolide also had high affinity for the dopamine D2 receptor, while only pergolide had significant, although moderate, affinity for the dopamine D1 receptor. Only pergolide had high potency and intrinsic activity at the dopamine D1 receptor for stimulating cyclic AMP accumulation. In addition, the potencies and efficacies of pergolide and bromocriptine, as well as that of dopamine, at the dopamine D1 receptor were increased in the presence of forskolin, an adenylate cyclase activator. All four compounds were highly potent agonists at dopamine D2 and D3 receptors, as measured in a mitogenesis assay. Bromocriptine was ten times more potent and pramipexole and ropinirole ten times less potent at the dopamine D2 than at the dopamine D3 receptor, whereas pergolide was equipotent at the two receptors. These results suggest that the activity of recently developed antiparkinsonian drugs at either the dopamine D1 or the dopamine D3 and not only the dopamine D2 receptors should be taken into account in analyses of their mechanisms of action in therapeutics.

MeSH terms

  • Animals
  • Antiparkinson Agents / pharmacology*
  • Benzazepines / metabolism
  • Benzazepines / pharmacology
  • Binding, Competitive / drug effects
  • CHO Cells
  • Cricetinae
  • Cyclic AMP / biosynthesis
  • Dopamine / metabolism
  • Dopamine / pharmacology
  • Dopamine Agonists / metabolism
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / metabolism
  • Dopamine Antagonists / pharmacology
  • Drug Evaluation
  • Humans
  • Hybrid Cells
  • Mitosis / drug effects
  • Radioligand Assay
  • Receptors, Dopamine D1 / drug effects*
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism
  • Recombinant Fusion Proteins / drug effects
  • Recombinant Fusion Proteins / genetics
  • Sulpiride / analogs & derivatives
  • Sulpiride / metabolism
  • Sulpiride / pharmacology
  • Tumor Cells, Cultured


  • Antiparkinson Agents
  • Benzazepines
  • Dopamine Agonists
  • Dopamine Antagonists
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Recombinant Fusion Proteins
  • iodosulpride
  • Sulpiride
  • Cyclic AMP
  • Dopamine