Adrenoceptor blocking effects of arotinolol, a new combined alpha- and beta-adrenoceptor blocking agent.

In isolated tissues and anesthetized animals, beta- and alpha-adrenoceptor blocking properties of arotinolol were studied in comparison with those of other typical adrenoceptor antagonists. The following order of beta-adrenoceptor blocking activities were obtained in isolated tissues: arotinolol = pindolol greater than propranolol = oxprenolol = alprenolol greater than or equal to labetalol for beta 1-adrenoceptors (guinea-pig right atrium) and pindolol = oxprenolol = arotinolol greater than propranolol greater than labetalol for beta 2-adrenoceptors (guinea-pig trachea). In anesthetized cats, arotinolol was about 9 and 25 times more potent than propranolol, about 30 and 100 times more potent than labetalol in blocking beta 1- and beta 2-adrenoceptors, respectively. Furthermore arotinolol showed a competitive antagonistic effect on phenylephrine-induced contraction of isolated rat aortic strips. The relative order of alpha 1-adrenoceptor blocking potencies was as follows: prazosin greater than phentolamine greater than labetalol greater than arotinolol = yohimbine. Presynaptic alpha 2-adrenoceptor blocking action of arotinolol was also assessed in isolated rat vas deferens and arotinolol was revealed to be a much weaker presynaptic alpha 2-adrenoceptor antagonist. In anesthetized rats arotinolol was 4-5 times less potent than labetalol and about 26 times less potent than phentolamine in blocking alpha 1-adrenoceptors. Thus, as for the selectivity for 2 subtypes of alpha-adrenoceptors, arotinolol showed a selectivity for alpha 1-adrenoceptors over presynaptic alpha 2-adrenoceptors.