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

Abstract

Abstract-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 Rossler method. Inhalation of 0.01 % of Ba598Br had an inhibitory effect against acetyl choline (ACh, 10 Sag/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 swum 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 ,tg/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 con tractions, 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.

Inhibitory Reflex during Bronchoconstrictions Induced by Histamine and Ascaris Suum Antigen.

“…The reflex tracheal constriction was also observed during the inhalation of Ascaris suum antigen. The antigen-induced bronchoconstriction was re duced by vagotomy or vagal blockade with nerve cooling (7,9). The present observation of the reflex component induced by antigen inhalation may indicate a prominent role of the vagal reflex in asthmatic airway constric tion.…”

Effects of flutropium on experimental models of drug- and allergy-induced rhinitis in guinea pigs.

“…The inhibitory action of flutropium was slightly stronger than that of atropine. The different inhibitory action between flutropium and atro pine may be due to the difference of the anti histaminergic activities as has already been re ported by Yanaura et al (14).…”

“…In addition to an anticholinergic action (14), flutropium can stabilize the cell mem brane (16) and has an antihistaminergic action (14,15). The anticholinergic action of flutro pium was stronger and longer lasting than that of atropine (14). Flutropium has been re ported to cause bronchodilation in ex perimental models of drug and allergy-in duced bronchoconstrictions in dogs (14).…”

“…The anticholinergic action of flutro pium was stronger and longer lasting than that of atropine (14). Flutropium has been re ported to cause bronchodilation in ex perimental models of drug and allergy-in duced bronchoconstrictions in dogs (14). However, no pharmacological study on the effects of flutropium on rhinitis has hitherto been performed.…”

“…Flutropium bromide (flutropium) is a new antiasthma drug possessing the quartemary ammonium salt structure of an atropine derivative. In addition to the anticho linergic action, flutropium has antihista minergic and antiallergic actions (14)(15)(16). However, there are very few experimental rhi nitis models in guinea pigs.…”