Comparison of inhibitory effects of CPU-86017 and its optical derivates on mouse blood pressure and rat aortic contraction

Abstract

Abstract: AIM: To compare the effects of III Class antiarrhythmic CPU-86017 ( p-chlorobenzyl-tetrahydroberberine) and its 12 optical derivates on mouse blood pressure and rat aortic contractile activity. METHODS: Zh-005 to zh-008 are 4 stereoisomers of p-nitrobenzyl-tetrahydroberberine, and zh-009 to zh-012 are 4 stereoisomers of N-benzyl-tetrohydroberberine.In this study, CPU-86017 or zh-005-zh-012 at dose of 3 mg/kg were i.v.in anaesthetized mice, and the blood pressure was monitored by arterial cannulation for 3 hours.CPU86017 or zh-001 to zh-004 (the 4 stereoisomers of CPU-86017) was administered in gradient dosage to rat aorta in vitro for evaluation the effects on aortic contraction induced by Phe and KCl. RESULTS: The least potency on blood pressure of CPU-86017 and zh-005-zh-012 was found by iv zh-006, which suggested the least side effect. By study of the inhibitory effects on rat aortic contraction of CPU86017 and zh-001 to zh-004, we found that the stereoisomers showed a stereoselectivity on suppressing the receptor related Ca²⁺ channel ( ROC), but not the voltage dependent Ca²⁺ channel (VOC). CONCLUSION: The configuration of C-13a in the structural formula of p-chlorobenzyl-tetrahydroberberine might be dominant to its affinity to α1A receptor.

Key words: CPU-86017, optical derivate, blood pressure, aortic contractile activity

CLC Number:

R965.2

FENG Yu, YANG Lin, DAI De-zai, ZHANG Can, DAI Yin. Comparison of inhibitory effects of CPU-86017 and its optical derivates on mouse blood pressure and rat aortic contraction[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(1): 23-27.

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