On the ionic mechanism of cyproheptadine-induced bradycardia in a rabbit sinoatrial node preparation.
The effects of cyproheptadine (0.1-10 microM) on the membrane potentials and currents of rabbit sinoatrial node were examined with the double-microelectrode voltage clamp technique. Cyproheptadine reduced the heart rate, maximum rate of depolarization and action potential amplitude. It also decreased the slope of phase 4 depolarization. On the current systems, cyproheptadine decreased the slow inward current (Isi), the time-dependent potassium outward current (Ik) and the hyperpolarization-activated current (Ih). The reduction of Isi was the major effect. Furthermore, Isi was progressively decreased by repetitive membrane depolarization during administration of cyproheptadine, an effect suggestive of frequency-dependent block of Isi. These electrophysiological observations indicate that cyproheptadine has a calcium antagonistic property, and additionally, decreases Ik and Ih in rabbit sinoatrial node.
Kotake
H
H
1st Department of Internal Medicine, Yonago, Japan.
Saitoh
M
M
Ogino
K
K
Hirai
S
S
Matsuoka
S
S
Hasegawa
J
J
Mashiba
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003533:Cyproheptadine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology*
D003533:Cyproheptadine