The beta 1- and beta 2-antagonist activity of betaxolol and timolol in the systemic circulation was studied ex-vivo after their ocular administration in thirty patients during cataract surgery. The patients received 40 microliters of 0.5% betaxolol or 0.25% timolol into the lower cul-de-sacs of both eyes. Blood samples were collected up to four h after instillation of the doses. Plasma concentrations of betaxolol and timolol were analyzed using a radioreceptor assay. The ex-vivo-beta 1-and beta 2-receptor occupancies corresponding drug plasma levels were calculated using radioligand binding techniques. The extent of beta 1-receptor occupancy of betaxolol in the systemic circulation was less than 20% and its beta 2-receptor occupancy was negligible. The extent of beta 1-receptor occupancy of timolol was about 65% and its beta 2-receptor occupancy about 80%. Because receptor occupancy is the basis of antagonist activity of beta-blocking agents, this study shows that the beta 1-antagonist activity of betaxolol in the systemic circulation is much less than that of timolol, and that its beta 2-antagonist activity is negligible. The study suggests that the reported side effects of betaxolol in patients with obstructive pulmonary diseases are not mediated via its beta 2-receptor blocking properties.

The effect of digoxin on both the negative inotropic action and the myocardial uptake of a new anthracycline antibiotic violamycin B1 has been studied in isolated guinea pig atria. In concentrations upto 2.0×10−7 M/l digoxin did not prevent the negative inotropic effect of violamycin B1 caused by the concentrations of 0.7 and 5.0×10−4 M/l. Corresponding to these findings, the uptake of violamycin B1 into the atrial tissue was not influenced by digoxin. However, violamycin B1 in the cardiotoxic concentration of 5.0×10−4 M/l decreased the atrial uptake of digoxin. It is suggested that no competition seems to exist in myocardial uptake of anthracycline antibiotics and cardiac glycosides.