Effects of a new antiarrhythmic compound SUN 1165 [N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride] on the sodium currents in isolated single rat ventricular cells.
The effects of a new antiarrhythmic compound, SUN 1165 (which resembles lidocaine in chemical structure) on sodium currents (INa) of enzymatically isolated, single rat ventricle cells were studied under current or voltage clamp conditions. A suction pipette technique was used for current injection and internal perfusion. Potassium currents were blocked by replacing K+ with Cs+ in the internal and external solutions, and calcium current by replacing Ca2+ with Co2+ in the external solution. When cells were stimulated infrequently (less than 1 HZ), SUN 1165 decreased INa without changing the position of the current-voltage curve. The inactivation curve of INa shifted to negative potentials along the voltage axis. The drug also produced an additional use-dependent block of INa, which depended on the frequency of the voltage clamp pulse. The effects of SUN 1165 on INa resemble those of lidocaine, although the relative importance of use-dependent action versus tonic blockade differs from that of lidocaine.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008839:Microelectrodes; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D008012:Lidocaine; D012964:Sodium; C042288:pilsicainide