Involvement of vagal pathway in the anti-secretory effect of a novel xanthine derivative.

The inhibitory action of a novel xanthine derivative, 3-ethyl-1-(6-hydroxy-6-methylheptyl)-7-propylxanthine (A90 6119) on gastric acid secretion was studied in rats. In conscious pylorus-ligated rats, A90 6119 (3 mg/kg intraduodenally, i.d.), inhibited gastric acid output stimulated by carbachol and by 2-deoxy-D-glucose by 49% and 100% respectively. Basal acid secretion was inhibited by 61% by 10 mg/kg, i.d. A90 6119. In urethane anesthetized stomach-lumen-perfused rats, A 90 6119 at 1 and 3 mg/kg, i.d. significantly reduced the acid secretion stimulated by 2-deoxy-D-glucose, by 83% and 100%, respectively. The stable thyrotropin-releasing hormone (TRH) analog, RX 77368, injected intracisternally (i.c.) at a 30 ng dose, induced concomitant increases in acid secretion and gastric mucosal blood flow. A90 6119 (10 micrograms/rat, i.c.) inhibited by 93% and 132% the increase in acid secretion and gastric mucosal blood flow induced by i.c. injection of TRH analog, respectively. These data suggest that the anti-secretory effect of A90 6119 involves inhibition of both central and peripheral vagal cholinergic pathways.