从远志中分离鉴定出1种多巴胺受体活性化合物

目的从中药远志中提取脑内多巴胺(DA)受体活性化合物。方法用体外的放射配体-受体结合和高压液相法提取、分离、纯化DA受体活性化合物,用核磁共振和质谱仪确定活性化合物的结构。结果提取、分离到1种四氢非洲防己胺的活性化合物。其在体外可抑制3H-SCH23390(DA1受体亚型)和3H-螺呱隆(DA2受体亚型)与大鼠纹状体细胞膜的结合,其IC50值分别为(0.75±0.08)μmol/L和(0.92±0.10)μmol/L。这种活性化合物还能抑制3H-呱唑嗪和大鼠大脑膜α1-肾上腺素受体的结合(IC50值为46μmol/L),但是不能改变3H-QNB及3H-muscimol对膜的结合。Scatchardplot分析显示此化合物对3H-SCH23390和3H-螺呱隆与纹状体细胞膜的结合的抑制作用是通过竞争性与非竞争性混合机制而实现的。结论远志中提取到的四氢非洲防己胺是脑内多巴胺受体的活性化合物,它的抑制作用是通过竞争性与非竞争性混合机制而实现的。

ISOLATION AND IDENTIFICATION OF TETRAHYDROCOLUMBAMINE AS A DOPAMINE RECEPTOR LIGAND FROM POLYGALA TENUlFOLIA WILLD

Objective: To isolate and purify the active compounds at the dopamine receptor from Chinese medicinal herb,Polygala Tenuifolia Willd. Methods: The extracts from Polygala Ten-uifolia Willd were isolated and identified by radio-receptor binding assay with HPLC methods. The chemical structures of the compound was identified by NMR and mass spectrometry. Results: One active compound,tetrahydrocolumbamine,was got and it inhibited the bindings of 3H-SCH23390 (DA1 subtype)and 3H-spiroperidol(DA2 subtype)to rat striatum membranes in vitro with IC50 values of (0.75±0.08) μmol/L and(0.92±0.10) μmol/L,respectively. The compound also inhibited the binding of prazosin to α1-adrenoceptor in vitro with IC50 value of 46 μmol/L. While it did not change the binding of ligands,3H-QNB and 3H-muscimol to rat cortex in vitro. Scatchard plot analysis showed a mixed competitive and noncompetitive inhibition by the compound on both 3H-SCH23390 and 3H-spiroperidol bindings to membranes from rat striatum. Conclusion: Tetrahydrocolumbamine from Chinese medicinal herb,Polygala Tenuifolia Willd is an active compound which inhibits the bindings of 3H-SCH23390 and 3H-spiroperidol to rat striatum membranes by a mixed competitive and noncom-petitive mechanisms.