title: In vivo antiarrhythmic profile of AP-792 assessed in different canine arrhythmia models.
abstract: 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.
authors.affiliation: Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan. akira_takahara@ajinomoto.com
authors.forename: A
authors.initials: A
authors.lastname: Takahara
authors.forename: A
authors.initials: A
authors.lastname: Hirasawa
authors.forename: H
authors.initials: H
authors.lastname: Dohmoto
authors.forename: M
authors.initials: M
authors.lastname: Shoji
authors.forename: R
authors.initials: R
authors.lastname: Yoshimoto
authors.forename: A
authors.initials: A
authors.lastname: Sugiyama
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: 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
chemical_list: C452621:AP792; D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D010880:Piperidines; D026941:Sodium Channel Blockers; D004837:Epinephrine