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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.
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