In vivo antiarrhythmic profile of AP-792 assessed in different canine arrhythmia models.
The antiarrhythmic effects of a novel antiarrhythmic drug AP-792, 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[4-cyclohexylbutyl]piperidine hydrochloride, were analyzed using the epinephrine-, digitalis- and two-stage coronary ligation-induced canine ventricular arrhythmia models. Intravenous administration of AP-792 (0.3 or 1.0 mg/kg) effectively suppressed each of the ventricular arrhythmias, an action that resembles that of a typical cardioselective Ca2+ channel blocker, AH-1058. The antiarrhythmic action of AP-792 was slow in onset and longer-lasting than those in our previous studies using more than 50 antiarrhythmic drugs, including Na+ and Ca2+ channel blockers. These results suggest that AP-792 can become a unique long-acting antiarrhythmic drug.
Takahara
A
A
Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan. akira_takahara@ajinomoto.com
Hirasawa
A
A
Dohmoto
H
H
Shoji
M
M
Yoshimoto
R
R
Sugiyama
A
A
Hashimoto
K
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004070:Digitalis / Q000009:adverse effects; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000009:adverse effects; D006352:Heart Ventricles / Q000187:drug effects*; D007275:Injections, Intravenous; D008026:Ligation / Q000009:adverse effects; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000494:pharmacology
C452621:AP792; D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D010880:Piperidines; D026941:Sodium Channel Blockers; D004837:Epinephrine