Combined effect of disopyramide and bethanechol: use of bethanechol to prevent anticholinergic side effects of disopyramide without reduction of antiarrhythmic efficacy.
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.
Konishi
T
T
National Sengokuso Hospital, Osaka, Japan.
Kadoya
M
M
Ikeguchi
S
S
Sakai
K
K
Tamamura
T
T
Kawai
C
C
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
D000889:Anti-Arrhythmia Agents; D001626:Bethanechol Compounds; D010276:Parasympatholytics; D004206:Disopyramide