Effects of R56865 on membrane currents in isolated ventricular cardiomyocytes of the guinea-pig.
In isolated heart muscle, the compound R56865 (N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2- benzothiazolamine) has been shown to protect against intoxication by cardiac glycosides. We studied the influence of R56865 on various membrane currents in single isolated ventricular cardiomyocytes of the guinea-pig. The sodium current, INa, was investigated at reduced extracellular Na+ (30 mM) in the presence of Cd2+ to block the calcium current, ICa, and with Cs+ substituted for K+ to reduce the K+ currents, IK. Under these conditions, R56865 concentration dependently decreased the peak INa with a half-maximum effect at about 1 microM. The steady state inactivation and normalized conductance of INa were not significantly different from the control. In 'normal' Tyrode solution, R56865 (10 microM) did not markedly reduce ICa, and did not affect the quasi steady state IK, which was taken as an index of K+ conductance. We conclude that R56865 possesses Na+ channel-blocking properties, whereas ICa and membrane K+ conductance were not influenced.
Pharmakologisches Institut, Universität-Gesamthochschule Essen, F.R.G.
H M
HM
Himmel
D
D
Wilhelm
U
U
Ravens
D000818:Animals; D052160:Benzothiazoles; D002104:Cadmium / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*
D052160:Benzothiazoles; D007473:Ion Channels; D010880:Piperidines; D015221:Potassium Channels; D015222:Sodium Channels; D013844:Thiazoles; D002104:Cadmium; D002586:Cesium; C054551:R 56865