[The effect of the benzimidazole derivative AR-L 115 BS on the activities of myocardial adenylate cyclase and phosphodiesterase preparations (author's transl)].
The effect of benzimidazole derivative 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazol[4,5-b]pyridine (AR-L115 BS) on phosphodiesterase (PDE) and adenylate cyclase (AC) preparations from myocardial tissue was investigated in vitro. The following results were obtained: 1. AR-L 115 BS inhibits the PDE activity comparable to papaverine in a concentration-dependent and non-competitive way. Its inhibitory potency is about 40 times less if compared to papaverine since the Ki-values found are 315 and 7.9 mumol/l, respectively. The concentration of AR-L 115 BS producing a maximal positive inotropic effect on the isolated guinea-pig atrial preparation was shown to be 316 mumol/l, i.e., in the same concentration range as the biochemical findings. 2. The basal activity of myocardial AC preparations from reserpine pretreated guinea-pigs was not significantly altered in the presence of AR-L 115 BS concentrations ranging from 10 to 200 mumol/l. In contrast, the isoprenaline (1-100 mumol/l) stimulated AC was concentration-dependently inhibited already by 1 to 10 mumol/l AR-L 115 BS.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology*; D010208:Papaverine / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology
D007093:Imidazoles; D012110:Reserpine; D010208:Papaverine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; C029758:sulmazole; D007545:Isoproterenol
Zur Wirkung des Benzimidazol-Derivates AR-L 115 BS auf die myokardiale Adenylatcyclase und Phosphodiesterase.