Effects of 8-(2-fluoroethyl)-3 alpha-hydroxy-1 alpha H, 5 alpha H-tropaniumbromide benzilate (Ba598Br) on allergy- and drug-induced asthmas.

The effects of Ba598Br, a new atropine derivative possessing a quarternary ammonium salt structure, on the canine airway, including its antiasthmatic effects, were investigated. The in vivo airway resistance was determined using the modified Konzett-Rössler method. Inhalation of 0.01% of Ba598Br had an inhibitory effect against acetyl-choline (ACh, 10 micrograms/kg i.v.)-evoked bronchoconstriction. The effect of Ba598Br was more powerful and longer lasting than that of the same dose of atropine. Pretreatment with Ba598Br (0.3%) and atropine (0.3%) by inhalation produced a remarkable inhibitory effect on the asthmatic bronchoconstriction induced by inhalation of Ascaris suum antigen in naturally sensitized dogs. In this case, Ba598Br showed a potency of approx. twice that of atropine as estimated from the inhibitory percent. On the other hand, in the case of posttreatment (drugs being inhaled after the antigen inhalation), both drugs showed inhibitory effects of equal degree. As for the effects on increased airway secretion at the time of asthmatic attack, both drugs inhibited the excessive secretions without any remarkable change in the viscosity of the secretions. Inhalation of 0.3% Ba598Br showed a powerful antihistamine action with respect to histamine (Hist, 3 micrograms/kg i.v.)-induced bronchoconstriction after the bilateral cervical vagi and superior laryngeal nerves were amputated. However, almost no effect could be observed with the same dose of atropine. Both Ba598Br and atropine showed relaxing actions of the same degree against ACh contraction on the isolated canine trachea, bronchus and bronchiole preparations, with a particularly strong relaxation being observed in the bronchiole. On the other hand, Ba598Br showed relaxing actions against histamine-induced contractions, which were more powerful than those of atropine, in the bronchus and bronchiole. From the above findings, it is suggested that the Ba598Br inhalation brings about antiasthmatic effects by its persistent, powerful anticholinergic actions and its transient but powerful antihistamine actions.