The binding of (±)-[3H]carazolol, a recently developed β-adrenergic antagonist of high potency, to rat cerebral cortical membranes is compared to the binding of (-)-[3H]dihydroalprenolol (3H-DHA). 3H-Carazolol binds saturably to cortical β-receptors with a KD of 0.15 nM, a value approximately four times lower than that for 3H-DHA. Considering that 3H-carazolol was used as the racemic mixture and 3H-DHA as the (-)-isomer, an equivalent formulation of 3H-carazolol would be 8-10 times more potent than 3H-DHA. This increased affinity can be explained by the observed two fold greater association rate constant and a two fold lower dissociation rate constant. The drug displacement profile of 3H-carazolol binding is very similar to that of 3H-DHA. 3H-Carazolol has equal displacements constants when binding is performed in calf cerebral cortex (which contains mainly β1 receptors) and calf cerebellum (which contains mainly β2 receptors), indicating that 3H-carazolol binds with equal affinity to β1 and β2 receptors. The percent free drug (i.e. unbound to serum proteins) for both carazolol and propranolol in rabbit serum is approximately 10%. At physiologically equivalent doses of carazolol and propranolol in the rabbit, there is no detectable free β-blocking activity at 15, 30 or 60 min after intravenous injection of carazolol, although substantial propranolol activity is detected. © 1979.
