The beta-
adrenoceptor blocking properties of
vaninolol ((+/-)4-[4'-(2-hydroxy-3-tert-butyl-aminopropoxy)-3'-methoxyphenyl]- 3-buten-2-one), derived from
vanillin, were first investigated under in vivo and in vitro conditions.
Vaninolol (0.1, 0.5, 1.0 mg/kg, i.v.), as well as
propranolol, produced a dose-dependent
bradycardia response and a sustained pressor action in
urethane-anesthetized normotensive rats.
Vaninolol inhibited the
tachycardia effects induced by (-)
isoproterenol, but had no blocking effect on the arterial pressor responses induced by
phenylephrine. These findings suggested that
vaninolol possessed beta-
adrenergic blocking activity, but was without alpha-
adrenergic blocking activity. In isolated guinea-pig tissues,
vaninolol antagonized (-)
isoproterenol-induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses in a concentration-dependent manner. The parallel shift to the right of the concentration-response curve of (-)
isoproterenol suggested that
vaninolol was a beta-
adrenoceptor competitive antagonist. The effect of
vaninolol was more potent on the atria than on tracheal tissues, indicating it had some beta 1-adrenoceptor selectivity. On the other hand, the order of the hydrophilicity was
atenolol >>
vaninolol >
propranolol. In addition,
vaninolol had a mild direct cardiac depression at high concentrations and was without intrinsic
sympathomimetic activity (ISA). Furthermore, binding characteristics of
vaninolol and other
beta-adrenoceptor antagonists were evaluated in [3H]
dihydroalprenolol binding to guinea-pig ventricular membranes. The order of potency of
beta-adrenoceptor antagonists in competing for the binding sites was (-)
propranolol >>
vaninolol > or =
atenolol. In conclusion,
vaninolol was found to be a selective beta 1-adrenoceptor antagonist with relatively low lipophilicity in comparison with
propranolol, devoid of ISA, and had a mild
myocardial depressant effect.