cyclovirobuxine-d and Ventricular-Fibrillation

To search for new compounds for the treatment of cardiovascular diseases by structural modification of cyclovirobuxine D.. According to rational drug design principle, a series of cyclovirobuxine D analogues were prepared, and their bioactivities were tested.. Ten new compounds were syntheized and confirmed by spectra.. Endurance lacking oxygen activity and antiarrhythmia effects of some analogues of cyclovirobuxine D were tested. Some compounds showed better activity than cyclovirobuxine D.

Topics: Anaerobic Threshold; Animals; Anti-Arrhythmia Agents; Buxus; Chloroform; Drugs, Chinese Herbal; Female; Male; Mice; Molecular Structure; Plants, Medicinal; Random Allocation; Ventricular Fibrillation

Cycloprotobuxine-A (CPB-A) 1-4 mg/kg (1/100-1/25 LD50) produced therapeutic and prophylactic effects which were found to be dose-dependent on experimental arrhythmias induced by BaCl2, aconitine and chloroform. Given at equitoxic doses, the anti-arrhythmic action of CPB-A was as potent as cyclovirobuxine-D (CVB-D) and amiodarone (Amio). However, its therapeutic index (LD50/ED50) was 1.8 times that of CVB-D and 1.2 times that of Amio. The most pronounced effects of CPB-A (0.3-30 mumol/L) on the electrophysiology of ventricular muscle of guinea pig were the lengthening of APD50, APD90 and ERP. This may contribute to its anti-arrhythmic action and suggests that CPB-A most likely belongs to class III anti-arrhythmic drugs (prolongation of APD). Perfused with the same concentration (3 mumol/L), CPB-A brought about more significant increases in APD50, APD90 and ERP than CVB-D and Amio did.

Topics: Action Potentials; Alkaloids; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Drugs, Chinese Herbal; Female; Guinea Pigs; Male; Mice; Rats; Rats, Inbred Strains; Ventricular Fibrillation