The binding of fluorocatecholamines to adrenergic and dopaminergic receptors in rat brain membranes

Abstract

2-Fluoronorepinephrine (IC 50 ≈0.7 μM) is a relatively selective ligand for displacement of radioactive dihydroalprenolol from β 1-adrenergic receptors in membrane preparations from rat cerebral cortex. It is less potent (IC 50 ≈10 μM) in displacing dihydroalprenolol from β 2-adrenergic receptors in rat cerebellar membranes and in displacing clonidine from α 2-adrenergic receptors in rat cerebral cortical membranes. It is much less potent (IC 50 > 100 μM) in displacing WB-4101 from α 1-adrenergic receptors in rat cerebral cortical membranes. In contrast, 6-fluoronorepinephrine is relatively selective for α-adrenergic receptors, being at least 50–200 times more potent at such receptors than at β-adrenergic receptors. 5-Fluoronorepinephrine like norepinephrine does not exhibit remarkable selectivity towards α- and β-adrenergic receptors. The 2-, 5- and 6-fluorodopamines are more potent ligands at α 1-adrenergic receptors than at α 2- and β-adrenergic receptors but the specificity is not markedly affected by the position of the fluorine substituent. The results suggest that the specificity exhibited by the 2- and 6-fluoronorepinephrine at adrenergic receptors is not primarily due to fluorine-induced changes in the physicochemical properties of the aromatic ring, but instead to stereoselective interactions of the ethanolamine side chain of norepinephrine with fluorine at either the 2- or 6-ring positron. The fluorodopamines like dopamine itself are more potent at dopaminergic than at α- or β-adrenergic receptors. The 2-, 5- and 6-fluorodopamines are all nearly equipotent with dopamine in the displacement of radioactive spiroperidol from dopaminergic receptors in membrane preparations from rat striatum, while the 2- and 6-fluorodopamine are somewhat less potent than dopamine or 5-fluorodopamine in displacement of radioactive apomorphine in striatal membranes.