Li L Q, Qu Z X, Wang Z M, Zeng Y L, Ding G S, Hu G J, Yang X Y
Sci Sin. 1979 Oct;22(10):1220-8.
Changrolin is 4-(3', 5'-bis[(N-pyrrolidinyl)methyl]-4'-hydroxyanilino)-quinazoline. It is a novel type of antidysrhythmic drug. It has been synthesized in 4 steps. According to our experiments, changrolin exhibited significant protective and therapeutic effects against experimental arrhythmias induced by aconitine or ouabain. It raised the electrical threshold of ventricular fibrillation. Intravenous injections in dogs and rabbits caused (i) a mild tachycardia followed by bradycardia; (ii) a prolongation of P-R interval and a widening of QRS complex in the electrocardiogram; (iii) a gradual hypotehsion; (iv) a slight weakening of cardiac functions; and (v) only moderate influences on the hearts of dogs and rabbits when the rate of infusion was less than 1 mg/min. Changrolin could be well absorbed by oral administration. Absorption appeared to be more rapid and complete by intramuscular injection. 14C-labelled changrolin was distributed mainly in the liver and the alimentary tract.
常咯啉是4-（3'，5'-双[（N-吡咯烷基）甲基]-4'-羟基苯胺基）喹唑啉。它是一种新型抗心律失常药物。它已通过4步合成。根据我们的实验，常咯啉对乌头碱或哇巴因诱发的实验性心律失常具有显著的保护和治疗作用。它提高了心室颤动的电阈值。对狗和兔子静脉注射导致：（i）先出现轻度心动过速，随后出现心动过缓；（ii）心电图中P-R间期延长和QRS波群增宽；（iii）逐渐出现低血压；（iv）心脏功能略有减弱；以及（v）当输注速率小于1mg/min时，对狗和兔子的心脏只有中度影响。常咯啉口服吸收良好。肌肉注射吸收似乎更快且更完全。14C标记的常咯啉主要分布在肝脏和消化道。
