Abstract

INTRODUCTION

IN VITRO PHARMACOLOGY

IN VIVO PHARMACOL

SUMMARY

REFERENCES

Discussion
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Tetrandrine, a new calcium channel blocker isolated from the Chinese medical herb, has been used clinically in China to treat angina and hypertension with good results. However, its chemical synthesis is difficult because of complicated structure and it has less potency and selectivity for blood vessels compared with dihydropyridines. In order to simplify the chemical structure of tetrandrine and find better therapeutic agents, we have synthesized and screened, using both [3H]-nitrendipine binding and biological assays, a series of benzyl- tetrahydroisoquinolines (half-molecules of tetrandrine). CPU-23, the most potent compound identified in this series, was found to inhibit KCl -induced contraction of rat aorta and displace [3H]-nitrendipine binding in rat cerebral cortical membranes with similar potency. CPU-23 also behaves as a simple competitive inhibitor at the [3H]-nitrendipine binding sites. Whole-cell patch-clamp experiments revealed that CPU-23 dose-dependently blocked L-type Ca2+ channels and delayed rectifier K+ channels in single smooth muscle cells isolated from rat tail artery and rabbit portal vein. In addition, it inhibited KCl-induced Ca2+ influx and action potential characteristics of myocardial preparation in vitro and induced hypotension and bradycardia in rat in vivo. It is indicated that CPU-23 is a novel potent calcium and delayed rectifier K+ channels blocker, which has therapeutic potentials of anti- hypertension and antiarrhythmics.

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Presentation Number SAdong0186
Keywords: CUP-23, Ca+2 channels, K+ Channels, vessels, hearts