A new kalium channel blocker of Chinese medicinal origin —Benzyltetrahydropalmatine hydrochloride

Summary

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 concentrationdependently prolonged the action potential duration (APD) and effective refractory period (FRP) between 1–100 μmol/L, the force of contraction remained unchanged.

• 3) In voltage clamp experiments BTHP 1–100 μmol/L inhibited in dose-dependent manner the I_k with IC₅₀ of 13 μmol/L and inhibited also I₅ 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.

I. BTHP showed a competitive α₁-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 α₁ and α₂-adrenoceptor.

The results from these experiments show that BTHP is a new K⁺ channel blocker of Chinese medicinal origin with α₁-adrenoceptor-blocking action.