Anti-arrhythmic effects of a new calcium antagonist, monatepil, AJ-2615, in experimental arrhythmic models [corrected].
1. To characterize the anti-arrhythmic properties of a new calcium antagonist, monatepil [corrected], AJ-2615, the preventive effects of AJ-2615 were compared with those of the existing calcium antagonists, diltiazem and verapamil, in experimental models of arrhythmia. 2. AJ-2615 (0.1-3.0 mg/kg, i.v.) suppressed ventricular arrhythmias induced by adrenaline (10 micrograms/kg, i.v.) in rats. AJ-2615 (0.1 mg/kg per min for 2 min, i.v.) also suppressed atrial tachycardia induced by aconitine (0.01% aconitine solution) in rats. 3. In these activities, AJ-2615 was comparable to or more potent than diltiazem and verapamil which are widely used for the treatment of arrhythmia. 4. In pro-arrhythmic activity, AJ-2615 was less potent than diltiazem and verapamil. 5. These results suggest that AJ-2615 would be a safer anti-arrhythmic agent, with less proarrhythmic liability than diltiazem and verapamil.
Yamamoto
T
T
Department of Pharmacology, Dainippon Pharmaceutical Co. Ltd, Osaka, Japan.
Hosoki
K
K
Karasawa
T
T
D000157:Aconitine / Q000633:toxicity; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D003988:Dibenzothiepins / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D004110:Diltiazem / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D004195:Disease Models, Animal; D004837:Epinephrine / Q000633:toxicity; D007275:Injections, Intravenous; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013610:Tachycardia / Q000188:drug therapy / Q000517:prevention & control; D014700:Verapamil / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity
D002121:Calcium Channel Blockers; D003988:Dibenzothiepins; D010879:Piperazines; D014700:Verapamil; D004110:Diltiazem; C067818:monatepil; D000157:Aconitine; D004837:Epinephrine