The blocking mechanism of sodium currents by a new class I antiarrhythmic drug, Ro 22-9194, in isolated guinea-pig ventricular myocytes.
1. Ro 22-9124 produced tonic block of sodium currents (INa) with a Hill coefficient of 1.01 and a dissociation constant of 0.12 microM at a holding potential of - 100 mV, and use-dependent block at 2 Hz in conjunction with an increase in pulse duration (5-300 msec). 2. Ro 22-9194 blocks INa, at least partially, due to binding to the activated state. 3. The course of recovery from the use-dependent block, which was not affected by the membrane potential, was 4.0 sec, suggesting that Ro 22-9194 belongs to the intermediate kinetic class I drugs and it probably acts via a hydrophobic pathway.
Karasaki
S
S
First Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan.
Sato
R
R
Katori
R
R
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002700:Chloramines / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology*; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D014105:Tosyl Compounds / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D002700:Chloramines; D011725:Pyridines; D015222:Sodium Channels; D014105:Tosyl Compounds; C016300:chloramine-T; C066993:Ro 22-9194