Anatagonism of the inhibitory effects of adenosine 5'-triphosphate on the isolated taenia of the guinea-pig caecum: structure-activity relationships within a series of isatogen derivatives.
1 A series of eight isatogen derivatives was studied on isolated tissues taken from guinea-pigs. The ability of the compounds to relax the taenia, to inhibit adenosine 5'-diphosphate (ADP)-stimulated respiration in mitochondria and to antagonize the inhibitory effects of adenosine 5'-triphosphate (ATP) on smooth muscle was measured. 2 All the derivatives inhibited ADP-stimulated respiration in mitochondria and relaxed the smooth muscle. These two effects were found to be significantly correlated. 3 Only half the compounds blocked the inhibitory effects of ATP, and all of these had a chemically reactive group (nitro, methoxy or pyridyl) in the 2'2-position. 2-2'-Pyridylisatogen was the most effective blocking agent. 4 The blockade of the inhibitory effects of ATP is not related to the other actions of the derivatives.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D002432:Cecum / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007510:Isatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D013329:Structure-Activity Relationship
D003497:Cyclic N-Oxides; D007211:Indoles; C017437:isatogen; D000244:Adenosine Diphosphate; D007510:Isatin; D000255:Adenosine Triphosphate