title: Combined effect of disopyramide and bethanechol: use of bethanechol to prevent anticholinergic side effects of disopyramide without reduction of antiarrhythmic efficacy.
abstract: Because bethanechol chloride (B) relieves the anticholinergic side effects of disopyramide (D), we examined the combined effects of D and B on the heart and urinary bladder. B was confirmed to counteract dose dependently the effect of D on the dog bladder. In the ventricular muscle, the combined electrophysiological effects (D + B) were additive, with no reduction in the effect of D. With the control value set as 100%, the decrease in the maximum rate of depolarization with 5 X 10(-6) g/ml D (90 +/- 6%) was not affected by the same dose of B (D + B: 84 +/- 14%). Moreover, the effective refractory period (ERP) was larger with D + B (128 +/- 12%) than with either B (109 +/- 9%, p less than 0.01) or D (115 +/- 11%, p less than 0.05). In contrast, in the atrial muscle and AV and SA nodes, B had marked acetylcholine-like effects. These were completely suppressed by the addition of D except for the atrial ERP with the highest tested concentration of B (5 X 10(-6) g/ml). In the latter case, the prolongation of ERP was minimal (B + D: 105 +/- 14%) as compared with D alone (130 +/- 15%). Since the plasma concentration of B after oral administration of a clinical dose is expected to be on the order of 10(-7) g/ml, no practical effect is anticipated. We conclude that B can be expected to counteract urination disorders caused by D without reducing D's antiarrhythmic efficacy.
authors: National Sengokuso Hospital, Osaka, Japan.
authors: T
authors: T
authors: Konishi
authors: M
authors: M
authors: Kadoya
authors: S
authors: S
authors: Ikeguchi
authors: K
authors: K
authors: Sakai
authors: T
authors: T
authors: Tamamura
authors: C
authors: C
authors: Kawai
mesh_terms: D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001283:Atrioventricular Node / Q000187:drug effects; D001626:Bethanechol Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004206:Disopyramide / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D001626:Bethanechol Compounds; D010276:Parasympatholytics; D004206:Disopyramide