[A study on the mechanism of the antiasthmatic effect of labetalol on experimental histamine-induced asthma].

The effect of labetalol (alpha- and beta- adrenoceptor blocking agent) on the respiratory organs of guinea pig was investigated in vivo and in vitro. The asthmatic symptoms which were induced by inhalation of histamine were relieved by pretreatment with labetalol (1-5 mg/kg, i.p.) in most cases. Propranolol, on the contrary, aggravated distinctly the histamine-induced asthma, although phentolamine and diphenhydramine relieved the asthma. Experiments carried out in vitro showed that labetalol relaxed the tonus of isolated tracheal preparation, shifting the histamine dose-response curve to the right and downward. The down shifting by labetalol was dose-dependent and much more sensitive than that by papaverine, and it disappeared after pretreatment of propranolol. Thus, it was considered that labetalol exerted a relaxing action on the tracheal preparation by a beta 2-adrenoceptor partial agonist action (intrinsic sympathomimetic activity, ISA). Since labetalol in high concentration also shifted the histamine dose-response curve parallel to the right as seen with phentolamine or diphenhydramine, it was considered that labetalol exerted not only an alpha-blocking action but also an antihistaminic action.