AN-132 block of cardiac sodium channels: a gate-related receptor analysis.
Based on the gate-related receptor hypothesis, an analysis of kinetics of AN-132, a new antiarrhythmic agent, blockade of cardiac sodium channels and the gate-related receptor which is bound by the drug was performed by computer simulation. Model-predicted apparent rates of onset of AN-132 (30 mumol/L) blocking were 0.051, 0.038, and 0.034 AP-1 at stimulation frequencies of 1.0, 2.0 and 3.0 Hz, respectively. The time constant of recovery from block by AN-132 at resting potential -90 mV was 39.5 s. These findings are in agreement with those experimental data documented. The analysis of gate-related receptor shows that AN-132 binds the inactivation gate-related receptor, and the binding and unbinding are modulated by the inactivation process.
Department of Pharmacology, Zhanjiang Medical College, Guangdong.
Y J
YJ
Wu
D C
DC
Fang
D000813:Anilides / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003198:Computer Simulation; D005029:Ethylenediamines / Q000494:pharmacology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008955:Models, Cardiovascular; D011955:Receptors, Drug; D015222:Sodium Channels / Q000187:drug effects*
C053205:3-(diisopropylaminoethylamino)-2',6'-dimethylpropionanilide, diphosphoric acid; D000813:Anilides; D000889:Anti-Arrhythmia Agents; D005029:Ethylenediamines; D011955:Receptors, Drug; D015222:Sodium Channels