[Effect of a new selective alpha 2 adrenergic blocker, midaglizole, on isolated airway smooth muscle].
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.
Mizobe
M
M
Second Department of Medicine, Teikyo University School of Medicine.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C032368:midaglizole; D007545:Isoproterenol