Frequency dependent prolongation of effective refractory period by a complex class III antiarrhythmic agent CPU-86017.
OBJECTIVE
To compare the prolongation of the effective refractory period (ERP) of a novel complex Class III agent CPU-86017 with compounds blocking INa (lorcainide, Lor), IK (dofetilide, Dof), ICa (verapamil, Ver) and a complex Class III multiple channel blocking agent (amiodarone, Ami) at different frequency levels.


METHODS
The ERP of the guinea pig right papillary muscle and the anoxic left atrial muscle treated with high K+ at pH 6.6-6.8, in concentrations ranging 0.03-30 micromol/L was compared at frequency levels ranging from 0.5-4.0 Hz.


RESULTS
CPU-86017 showed a positive frequency dependence (PFD) with respect to ERP in the papillary muscles and a mild reverse frequency dependence (RFD) in the diseased atrium. The potency of ERP prolonging effect of various agents at 4.0 Hz was Dof > CPU-86017 > Ver > Ami > Lor, and Dof > CPU-86017 > Ami > Lor > Ver in the normal papillary and diseased atrial muscle, respectively.


CONCLUSIONS
The profile and potency of prolonging the ERP by CPU-86017 is similar to Dof which blocks IKr in the diseased atrium, and to Ver which blocks ICa in guinea pig ventricle.
Li
H T
HT
Research Division of Pharmacology, Department of Pharmaceutical Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Wang
Y Q
YQ
Dai
D Z
DZ
Kong
R Z
RZ
D000638:Amiodarone / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D044482:Benzeneacetamides; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
C400084:4-chlorobenzyltetrahydroberberine; D000889:Anti-Arrhythmia Agents; D044482:Benzeneacetamides; D002121:Calcium Channel Blockers; D010627:Phenethylamines; D010880:Piperidines; D026902:Potassium Channel Blockers; D013449:Sulfonamides; D001599:Berberine; D014700:Verapamil; C015970:lorcainide; D000638:Amiodarone; C063533:dofetilide