Agonist and antagonist properties of benzazepine and thienopyridine derivatives at the D1 dopamine receptor

Neuropharmacology. 1989 Apr;28(4):401-5. doi: 10.1016/0028-3908(89)90036-1.


Nine structurally related 1-phenyl-1H-3-benzazepine derivatives and two thienopyridines were tested for agonist and antagonist properties at the adenylate cyclase-coupled D1 dopamine receptor in homogenates of the striatum of the rat. The benzazepines SK&F 77434 and SK&F 82958, both of which contain a catechol ring, were agonists; the intrinsic activity of SK&F 77434 was similar to that of SK&F 38393, whereas SK&F 82958 was a full agonist. The remaining benzazepines inhibited the stimulation of adenylate cyclase by dopamine. Antagonist potency depended on the nature of the substituent at position 7 of the benzazepine molecule, 7-halogen compounds being the most potent. The Ki values, obtained from analysis of the antagonism of dopamine-stimulated adenylate cyclase, were significantly correlated with the Ki values for displacement of D1 ligands in binding experiments. Furthermore, antagonist activity of the resolved racemic benzazepine SK&F 83566 resided almost exclusively in the R-enantiomer. The thienopyridine derivatives SK&F 89641 and SK&F 89145 were partial agonists with greater efficacies than SK&F 38393.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Animals
  • Benzazepines / pharmacology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / enzymology
  • Dopamine Agents / pharmacology*
  • In Vitro Techniques
  • Male
  • Pyridines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Structure-Activity Relationship


  • Adenylyl Cyclase Inhibitors
  • Benzazepines
  • Dopamine Agents
  • Pyridines
  • Receptors, Dopamine