Comparison of anticholinergic effects of cibenzoline, disopyramide, and atropine.
The anticholinergic effects of cibenzoline, disopyramide, and atropine were compared on experimental models. Using inhibition of specific binding of 3H-quinuclidinyl benzylate (3H-QNB) in rat heart and cerebral cortex, Ki values were 15.8 +/- 1.6, 12 +/- 3.5, and 0.013 +/- 0.001 microM, respectively, for heart membranes and 31.6 +/- 1.5, 7.8 +/- 1.3, and 0.006 +/- 0.001 microM, respectively, for cerebral cortex membranes. In isolated guinea pig ileum, disopyramide was about 15 times more anticholinergic than cibenzoline but about 900 times less so than atropine. In anesthetized dogs, the three drugs administered by intravenous bolus reduced bradycardia caused by vagal stimulation. The effect of cibenzoline at 7 mg/kg i.v. (double the antiarrhythmic dose) was approximately the same as that of disopyramide at 2.5 mg/kg (half the antiarrhythmic dose). The drugs were infused for 1 h at 0.17 mg/kg/h for atropine, 11.6 mg/kg/h for disopyramide, and 5.5 mg/kg/h for cibenzoline. The maximal inhibition of the vagal stimulation was 98, 95, and 52%, respectively, for the three drugs. In nonanesthetized dogs, inhibition of the vagal-tone-induced tachycardia reached 33 +/- 4, 134 +/- 20, and 206 +/- 19% for cibenzoline, disopyramide and atropine, respectively. These results show cibenzoline to exert less potent anticholinergic effects than disopyramide.
Cazes
M
M
Département Biologie, Laboratoires UPSA, Rueil-Malmaison, France.
Chassaing
C
C
Martinet
M
M
Cloarec
A
A
Provost
D
D
Boucher
M
M
Duchêne-Marullaz
P
P
D000818:Animals; D001285:Atropine / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004206:Disopyramide / Q000378:metabolism / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010276:Parasympatholytics; D051381:Rats; D011919:Rats, Inbred Strains; D014630:Vagus Nerve / Q000502:physiology
D007093:Imidazoles; D010276:Parasympatholytics; D001285:Atropine; D004206:Disopyramide; C032151:cifenline