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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。
Objective To extract dopamine (DA) receptor active compounds from the brain of Polygalaceae. Methods The active compound of DA receptor was extracted, isolated and purified by in vitro radioligand-receptor binding and high pressure liquid phase method. The structure of the active compound was determined by nuclear magnetic resonance and mass spectrometry. Results An active compound of tetrahydroflavoxamine was extracted and isolated. It inhibits the binding of 3H-SCH23390 (DA1 receptor subtype) and 3H-spiroprolonger (DA2 receptor subtype) to rat striatal cell membrane in vitro with IC50 values of (0.75 ± 0.08) μmol/l. L and (0.92 ± 0.10) μmol/L. The active compound also inhibits the binding of 3H-carbazin to the rat brain membrane α1-adrenergic receptor (IC50 value of 46 μmol/L) but does not alter the binding of 3H-QNB and 3H-muscimol to the membrane. Scatchardplot analysis showed that the inhibitory effect of this compound on the binding of 3H-SCH23390 and 3H-spiroprost to the striatal cell membrane was achieved through a competitive and non-competitive mixing mechanism. Conclusion Tetrahydropalmonine extracted from Polygala tenuifolia is an active compound of dopamine receptors in the brain. Its inhibitory effect is achieved through a combination of competitive and non-competitive mechanisms.