EFFECTS OF S-9977-2 ON THE GUINEA-PIG ISOLATED TRACHEA AND THE HUMAN ISOLATED BRONCHUS

The effects of S 9977-2, a new compound which belongs to the trimethylxanthine family and has shown in vivo promnesic activity and in vitro acetylcholinesterase activities inhibition, were studied on the guinea pig isolated trachea and on human isolated bronchi. On the guinea pig isolated trachea, S 9977-2 in concentrations of 10(-7)-10(-4) M potentiated the contractile effect of acetylcholine. The potency of acetylcholine was increased 3.39, 4.26, 9.54, and 13.18 fold with concentrations of 10(-7), 10(-6), 10(-5), and 10(-4) M, respectively. The maximum effect of acetylcholine was not modified. S 9977-2 did not potentiate the effects of carbachol or pilocarpine. Under similar conditions, eserine (10(-8) and 10(-6) M) and tacrine (10(-8)-10(-6) M) also potentiated the effects of acetyl choline.The potentiating effect of these two substances was stronger than that of S 9977-2, with a 44.7 fold increase for eserine (10(-7) M) and a 64.6 fold increase for tacrine (10(-6) M). However, both eserine and tacrine had a contractile effect of their own on the guinea pig isolated trachea, whereas S 9977-2 had no such effect. On the human isolated bronchus, S 9977-2 at a concentration of 10(-5) M produced a 19.1 fold increase of acetylcholine effects. On the guinea pig isolated trachea, the effects of S 9977-2 vs. acetylcholine were not modified by epithelium removal. They were increased by pretreatment with indomethacin 10(-6) M. In very high concentrations (10(-4) and/or 10(-3) M), S 9977-2 reduced the effects of histamine and those of serotonin on the guinea pig isolated trachea. S 9977-2 had no effect on the contractile action of potassium chloride or on the relaxant action of adenosine. The results suggest that in the airway smooth muscle S 9977-2 partially inhibits acetylcholinesterase and/or pseudocholinesterase activity.