Cetamolol: cardiovascular effects of a new cardioselective β-adrenoceptor blocker possessing partial agonistic activity and lacking membrane-stabilizing activity

Abstract

The cardiovascular effects of cetamolol, a new β-adrenoceptor blocker, were studied in the anesthetized dog and cat and in the conscious dog and monkey. The compound was compared with other β-blockers known to possess various degrees of cardioselectivity, partial agonistic effects, and membrane-stabilizing activity. In the anesthetized open-chest dog, cetamolol and pindolol produced similar cardiovascular effects in that the partial agonistic activity predominated over the blockade of β-adrenoceptors. The partial agonistic activity of pindolol was greater than that of cetamolol. Unlike pindolol, cetamolol had no significant vasodilating property. However, the β-blocking effects of these two drugs predominated in the anesthetized closed-chest dog, conscious dog and monkey. Atenolol, nadolol, and propranolol, which lack partial agonistic activity, produced cardiovascular changes characteristic of this type of β-blocker in the animal preparation in which they were tested. In the anesthetized cat, comparison of the mean effective doses for the heart rate and blood pressure responses induced by isoproterenol showed that cetamolol was more cardioselective than metoprolol but less than acebutolol and atenolol. Evidence of the cardioselectivity of cetamolol was also obtained in the anesthetized closed-chest dog, although the degree of cardioselectivity of both cetamolol and atenolol was less marked than in the cat. When given orally to the conscious dog and monkey, cetamolol appeared to be well absorbed. The peak effect was observed after 1 – 2 h and persisted for the 5-h test period. It is concluded that cetamolol is a potent β-blocker with a moderate degree of partial agonistic activity and cardioselectivity in in vivo experiments.