The role of alpha-
adrenoceptors in
asthma is still unclear. However, several studies have shown bronchodilatation after single doses of different alpha-
adrenoceptor antagonists in patient's with
asthma. The clinical efficacy of
midaglizole, a new selective alpha 2 blocker was demonstrated by a more recent investigation. The present investigation was carried out to examine the effects of
midaglizole on isolated airway smooth muscle obtained from humans and guinea pigs. Human bronchial smooth muscle was relaxed in a dose-dependent manner by
midaglizole. EC50, molar concentration of
midaglizole required to produce 50% reversal of
carbachol-induced pre-contraction was (6.0 +/- 0.19) X 10(-5) M.
Isoproterenol (5 X 10(-10) M) and
midaglizole (3 X 10(-5) M) produced 30.0 +/- 9.5% and 40.8 +/- 7.0% of maximal relaxation, respectively. However, they produced almost 100% of maximal relaxation when used together.
Isoproterenol, in combination with
midaglizole, was associated with a significant increase of human bronchial relaxation as compared to either of the drugs singly. The same findings were obtained when the drugs were used on the guinea pig trachea.
Midaglizole had no effect on the binding of the radiolabeled
beta adrenergic antagonist [3H]
dihydroalprenolol to particulates prepared from the lung.
Propranolol did not inhibit the relaxant effect of
midaglizole on airway smooth muscle. These results suggest that
midaglizole may be effective for the treatment of
asthma.