[Hemodynamic effects of medroxalol in the anesthetized dog. Relation between adrenolytic properties and plasma...

Hemodynamic properties of medroxalol (MDL), a new alpha-and-beta adrenoceptor antagonistic drug, were studied in eight pentobarbital-anesthetized (open chest) dogs. MDL was injected in three doses (1.5, 3.0 and 9.0 mg/kg i.v.) at one hour intervals. A control group (n = 5) received three successive vehicle injections at the same time intervals. Heart rate, systolic and diastolic arterial pressure, cardiac output and stroke volume (using an intrathoracic flowmeter), and peripheral resistance were recorded 45 min before the first injection and 15 min after each administration. Isoproterenol (ISP) and neosynephrine (NSP) dose-response curves were recorded before the first dose and after each injection in both group. Log-linear regression analyses were used to estimate the ISP chronotropic dose 25 (DC 25) and the ISP barotropic dose 30 (DB 30). The results show that medroxalol possesses beta-adrenoreceptor antagonistic properties which are 35 times greater than its alpha-antagonistic properties. Beta-blockade was evidenced by bradycardia and increase in DC 25, beginning at the first dose used. Alpha-blockade was not significant at that first dose and therefore cannot alone explain the strong hypotension observed. All these effects were related to the plasma-concentration of MDL.