Comparison of the cardiac electrophysiological effects between doxazosin and bunazosin.
In Langendorff-perfused adult rat heart with constant pressure at 80 mmHg, we found doxazosin, an alpha(1) adrenoceptor blocker, at 10 muM prolonged PR interval and induced occasional arrhythmia followed by complete inhibition of the sinus rhythm, whereas bunazosin, another alpha(1)-blocker, at same concentration did not. The results of voltage-clamp study showed that, at the concentration of 10 muM, doxazosin inhibited I (Na), I ( (Ca,L) ), I (to), and Iss without changing I (k1) but bunazosin only inhibited I ( (Ca,L) ) about 30%. Doxazosin also caused markedly negative shift of the I (Na) inactivation curve. In current-clamp study, doxazosin prolonged action potential duration in association with the decreased action potential amplitude and upstroke velocity, whereas bunazosin did not. We hypothesize that doxazosin-induced arrhythmia may result from the heterogeneous or different level of I ( (Ca,L) ) blockade of AV nodal tissue. In conclusion, the present study suggests that bunazosin is safer than doxazosin for long-term treatment in view of electrophysiological effect. However, the underlying mechanism of doxazosin induced nodal arrhythmia is still needed to be determined.
Lee
An-Sheng
AS
Institute of Pharmacology, College of Medicine, National Taiwan University, No.1, Sec.1, Jen-Ai Rd., Taipei 100, Taiwan, ROC.
Chen
Wen-Pin
WP
Su
Ming-Jai
MJ
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D054849:Cardiac Electrophysiology; D017292:Doxazosin / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions; D006321:Heart / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000009:adverse effects*; D051381:Rats
D007473:Ion Channels; D011799:Quinazolines; C018176:bunazosin; D017292:Doxazosin