ZINGERONOLOL - A NEWLY DEVELOPED BETA-ADRENERGIC BLOCKING-AGENT DERIVED FROM ZINGERONE, A PUNGENT PRINCIPLE OF GINGER

Zingeronolol (0.1, 0.5, 1.0 mg/kg, i.v.) produced a dose-dependent bra dycardia response and a presser action in urethane-anaesthetized normo tensive rats. Zingeronolol inhibited the tachycardia effects induced b y (-)isoproterenol, but did not show any blocking effect on the arteri al presser responses induced by phenylephrine. These findings clearly suggested that zingeronolol had a beta-adrenergic blocking activity, n evertheless it did not involve an alpha-adrenergic blocking activity. In organ bath studies, zingeronolol antagonized (-)isoproterenol-induc ed positive chronotropic effects in isolated guinea-pig right atria an d relaxation responses in rat uteri in a concentration-dependent manne r. The parallel shift to the right of the concentration-response curve of (-)isoproterenol suggested that zingeronolol was a beta-adrenocept or competitive antagonist. The apparent pA(2) values for zingeronolol on atria and uteri were 7.53 +/- 0.07 and 6.81 +/- 0.05, respectively. Zingeronolol was more potent on the atria than on uterine tissues ind icating that it possessed some beta(1)-adrenoceptor selectivity. Bindi ng characteristics of zingeronolol and various beta-adrenoceptor antag onists were evaluated in [H-3]dihydro-alprenolol ([H-3]DHA) binding to guinea-pig ventricular membranes. The IC50 values for (-)propranolol, zingeronolol and atenolol were 0.009 +/- 0.002, 5.2 +/- 1.1 and 6.5 /- 1.0 (mu M), respectively. On the other hand, zingeronolol exhibited a mild direct cardiac depression at high concentrations and was witho ut intrinsic sympathomimetic activity (ISA).