1. Agonist and antagonist properties of benzazepine and thienopyridine derivatives at the D1 dopamine receptor.
- Author
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O'Boyle KM, Gaitanopoulos DE, Brenner M, and Waddington JL
- Subjects
- Adenylyl Cyclase Inhibitors, Animals, Corpus Striatum drug effects, Corpus Striatum enzymology, In Vitro Techniques, Male, Rats, Rats, Inbred Strains, Structure-Activity Relationship, Benzazepines pharmacology, Dopamine Agents pharmacology, Pyridines pharmacology, Receptors, Dopamine drug effects
- Abstract
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.
- Published
- 1989
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