Bronchodilator and other pharmacological activities of R-836 (2,5-diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c]pyrimidin e)

The bronchodilator activity of R-386 (2,5-diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c]pyrimidine) was demonstrated in isolated guinea-pig tracheal preparations and in vivo in dogs, guinea-pigs and rats. Guinea-pig tracheal preparations contracted by histamine, acetylcholine, BaCl2, leukotriene C4 or antigen were relaxed 50% by concentrations (IC-50 values) of R-836 of approximately 0.3 microgram/ml (10(-6) M) in all cases. In the conscious guinea-pig, oral or i.p. administration of R-836 prevented asphyxial collapse, death or dyspneic changes produced by histamine, antigen of LTC4. In anesthetized guinea-pigs, R-836 reduced bronchoconstriction produced by antigen or PAF (Konzett-Rössler preparation). In the dog, i.v. or intraduodenal administration of R-836 reduced bronchoconstriction produced by methacholine or histamine. In the rat, i.p. administration of R-836 reduced bronchoconstriction produced by 5-HT or antigenic challenge. In these in vivo models, when direct comparisons were made, R-836 was estimated to possess 2 to 3 times the potency of theophylline. R-836, at doses 80 times those necessary to produce bronchodilation, had no effect on blood pressure or heart rate of guinea-pigs. R-836 was not a CNS stimulant in mice, was not diuretic in rats, only marginally inhibited adenosine-induced responses in mice and guinea-pigs and was a weak inhibitor of phosphodiesterase in vitro.