Effects of 5-HT(4) receptor agonist prokinetic agents on the action potential parameters of isolated rabbit myocardium.
The effects of TS-951, a novel gastrointestinal prokinetic agent with 5-HT(4) receptor agonistic action, on the action potential parameters of isolated rabbit Purkinje fiber, ventricular muscle and sinoatrial node, and on the spontaneously beating rates of isolated rabbit right atria were compared with those of cisapride. TS-951 had no effect on the action potential parameters in both rabbit Purkinje fiber and ventricular muscle preparations. However, cisapride significantly prolonged action potential duration (APD) in both preparations. Both TS-951 and cisapride produced a negative chronotropic effect in rabbit right atria; TS-951 and cisapride at 3 x 10(-5) mol/l reduced the beating rate by about 20 and 40%, respectively. In the sinoatrial node preparations, TS-951 (3 x 10(-5) mol/l) as well as cisapride (10(-6) mol/l) prolonged cycle length and APD and reduced the diastolic depolarization rate. These results indicate that TS-951 does not appear to possess electrophysiological features leading to cardiotoxicity such as QT prolongation and, thus, torsades de pointes in common with cisapride.
Noguchi
K
K
Pharmacology Laboratory, Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co., Ohmiya, Saitama, Japan. s15922@ccm.taisho.co.jp
Ito
C
C
Isobe
Y
Y
Fukushima
K
K
Tanaka
Y
Y
Tanaka
H
H
Shigenobu
K
K
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D020117:Cisapride / Q000737:chemistry / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D011804:Quinolines; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044422:Receptors, Serotonin, 5-HT4; D017366:Serotonin Receptor Agonists / Q000737:chemistry / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology; D016276:Ventricular Function
D011804:Quinolines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C426443:TS951; D044422:Receptors, Serotonin, 5-HT4; D020117:Cisapride