Antiarrhythmic effects of LR-A/113 a new calcium antagonistic drug.
LR-A/113 is a benzothiazepine drug similar to diltiazem with Ca(2+)-antagonist properties. Our previous studies showed that LR-A/113 determines anthypertensive effects comparable to diltiazem in normotensive and hypertensive rats. The aim of this study is to determine LR-A/113 effects respect to verapamil and diltiazem on CaCl2, aconitine and ouabain arrhythmias. Experiments were carried out on normotensive anesthetized rats and guinea pigs treated with CaCl2, aconitine and ouabaine and pretreated or not with verapamil, diltiazem or LR-A/113. Verapamil, diltiazem and LR-A/113, significantly delayed onset of arrhythmias and cardiac standstill induced by CaCl2 and aconitine. Moreover, pretreatments with verapamil, diltiazem or LR-A/113 reduced occurrence of arrhythmias in animals. In our models of arrhythmias LR-A/113 showed a significant antiarrhythmic effect of a magnitude almost similar to diltiazem but lower than for verapamil.
Stella
L
L
Institute of Pharmacology and Toxicology Faculty of Medicine, University of Naples, Italy.
de Novellis
V
V
Vacca
C
C
Guarino
A
A
Cantoni
V
V
Fici
F
F
Rossi
F
F
D000157:Aconitine; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010042:Ouabain; D051381:Rats; D017207:Rats, Sprague-Dawley
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D010042:Ouabain; C085176:siratiazem; D004110:Diltiazem; D002122:Calcium Chloride; D000157:Aconitine