目的 研究吡咯里嗪類ML-3000及其兩種NO供體衍生物ML-4000和ML-5000對(duì)人P450同工酶CYP2D6、CYP1A2、CYP2C9、CYP2C19和CYP3A4的體外抑制作用。方法 采用Gentest公司的高通量P450酶抑制劑篩選試劑盒（High throughput Inhibitor Screening Kit），測(cè)定ML-3000、ML-4000和ML-5000對(duì)五種P450同工酶CYP2D6、CYP1A2、CYP2C9、CYP2C19和CYP3A4的體外抑制作用。結(jié)果 ML-3000、ML-4000和ML-5000抑制CYP3A4的IC₅₀分別為7.07、0.40、2.82 μmol/L，對(duì)其他4個(gè)酶（CYP1A2、CYP2D6、CYP2C9和CYP2C19）的IC₅₀均大于10 μmol/L。結(jié)論 3種化合物對(duì)CYP3A4活力均有抑制作用，其中ML-4000的抑制能力最強(qiáng)。3種化合物對(duì)其他4個(gè)酶基本沒(méi)有抑制作用。

Objective To investigate the inhibition of ML-3000 and two NO donor derivatives in pyrrolizine on five human cytochrome P450 isozymes CYP2D6, CYP1A2, CYP2C9, CYP2C19, and CYP3A4. Methods Inhibition of ML-3000, ML-4000, and ML-5000 on five human cytochrome P450 isozymes CYP2D6, CYP1A2, CYP2C9, CYP2C19, and CYP3A4 was determined with High Throughput Inhibitor Sceening Kit. Results IC₅₀ values of ML-3000, ML-4000, and ML-5000 to CYP3A4 were 7.07, 0.40, and 2.82 μmol/L, respectively. IC₅₀ values of ML-3000, ML-4000, and ML-5000 to others were more than 10 μmol/L. Conclusion Three compounds have the inhibitory effects on CYP3A4. Among them, ML-4000 has the strongest inhibition. The three compounds show no inhibition on the other four enzymes.