A new kalium channel blocker of Chinese medicinal origin--benzyltetrahydropalmatine hydrochloride.
Benzyltetrahydropalmatine hydrochloride (BTHP) exhibited antiarrhythmic action in animal models. I. Electrophysiological effects of BTHP were investigated in various heart preparations. 1) BTHP markedly prolonged functional refractory period and inhibited adrenaline-induced automaticity. It decreased spontaneously beating rate of right atrium and abolished ouabain-induced delayed afterdepolarization and triggered activity of papillary muscle. 2) In standard microelectrode and contractility experiments BTHP concentration-dependently prolonged the action potential duration (APD) and effective refractory period (FRP) between 1-100 mumol/L; the force of contraction remained unchanged. 3) In voltage clamp experiments BTHP 1-100 mumol/L inhibited in dose-dependent manner the Ik with IC50 of 13 mumol/L and inhibited also Is at high concentration. 4) In monophasic action potential (MAP) of feline ventricle MAPD50 and MAPD90 were prolonged by BTHP in normal myocardium, and shortened APD induced by ischemia and reperfusion was restored to normal level. 5) In ECG and His-bundle electrogram heart rate was reduced; P-R and A-H interval were prolonged, but H-V interval and V duration were unaffected. II. BTHP showed a competitive alpha 1-adrenoceptor-blocking effect with pA2 value of 5.8 and 5.86 in rat anococcygeus muscle and rabbit aortic strips respectively. Radioligand binding assays showed that BTHP had affinity for both alpha 1 and alpha 2-adrenoceptor. The results from these experiments show that BTHP is a new K+ channel blocker of Chinese medicinal origin with alpha 1-adrenoceptor-blocking action.
Yao
W X
WX
Department of Pharmacology, Tongji Medical University, Wuhan.
Xia
G J
GJ
Zhang
J S
JS
Zeng
W Z
WZ
Zhang
S D
SD
Jiang
M X
MX
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000032:analysis*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D012756:Sheep
D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D001600:Berberine Alkaloids; D004365:Drugs, Chinese Herbal; D015221:Potassium Channels; C060778:benzyltetrahydropalmatine