Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure.

Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

大狼毒三萜类化学成分的研究

自大戟科(Euphorbiaceae)植物大狼毒(Euphorbia nematocypha Hand—Mazz)根的乙醇提取物的苯溶解部分,经20%AgNO₃硅胶层析,分离得到七个三萜类成分。根据光谱(IR,EIMS,¹H—NMR和¹³C—NMR)和化学方法,确定其中一个化合物为新化合物,命名为大狼毒醇(nematocyphol,Ⅳa),其它化合物为已知物:印度荆芥醇乙酸酯(nepehinol acetate Ⅰ),日尔曼醇乙酸酯(germanicol acetate Ⅱ),大戟醇(euphol,Ⅲ),蒲公英醇(taraxasterol,Ⅴa),24-亚甲基环阿尔廷醇(24-methylenecycloartanol,Ⅴa)和印度荆芥醇(nepehinol,Ⅶa)。这些化合物均为首次从大狼毒中得到。