Connacher A A, Jung R T, Mitchell P E
Department of Medicine, Ninewells Hospital and Medical School, Dundee.
Br Med J (Clin Res Ed). 1988 Apr 30;296(6631):1217-20. doi: 10.1136/bmj.296.6631.1217.
A double blind placebo controlled study was carried out in 40 subjects newly referred for treatment for obesity to determine the effects of the new thermogenic beta adrenoceptor agonist BRL 26830A. The subjects were randomised to receive either BRL 26830A, 200 mg daily for two weeks then 400 mg daily, or placebo for 18 weeks, and all were instructed to follow a 3.35 MJ diet that was low in fat and high in fibre. Weight loss was 15.4 (SD 6.6) kg in subjects given BRL 26830A compared with 10.0 (5.9) kg in those given placebo (p = 0.02). The relative weight loss was 0.93 (0.39%) a week with BRL 26830A and 0.61 (0.38)% with placebo (p = 0.02). Urinary excretion of nitrogen was similar in both groups, whereas measurements of skinfold thickness indicated a 4.1 kg difference in the amount of fat lost, suggesting that weight loss with BRL 26830A was mainly from adipose and not lean tissue. BRL 26830A had no effect on resting pulse rate or pressor effects on either diastolic or systolic blood pressure. No significant differences were found between the two groups in serum cholesterol concentration, percentage of high density lipoprotein cholesterol, plasma concentrations of glucose and insulin, the ratio of glucose to insulin, serum concentrations of triiodothyronine and thyroxine, and creatinine clearance. Short term administration of BRL 26830A to six subjects who had taken the drug for 18 weeks showed that the expenditure of energy increased by 11.6% during the second hour after administration, which suggests that BRL 26830A may enhance weight loss thermogenically. BRL 26830A may be a useful drug in the treatment of obesity.
对40名新转诊接受肥胖治疗的受试者进行了一项双盲安慰剂对照研究,以确定新型产热β肾上腺素能受体激动剂BRL 26830A的效果。受试者被随机分为两组,一组每天服用200毫克BRL 26830A,持续两周,然后每天服用400毫克,另一组服用安慰剂,为期18周,所有受试者均被要求遵循低脂肪、高纤维的3.35兆焦耳饮食。服用BRL 26830A的受试者体重减轻了15.4(标准差6.6)千克,而服用安慰剂的受试者体重减轻了10.0(5.9)千克(p = 0.02)。服用BRL26830A时相对体重减轻率为每周0.93(0.39%),服用安慰剂时为0.61(0.38)%(p = 0.02)。两组的尿氮排泄量相似,而皮褶厚度测量表明,脂肪减少量相差4.1千克,这表明服用BRL 26830A导致的体重减轻主要来自脂肪组织而非瘦组织。BRL 26830A对静息脉搏率或舒张压及收缩压的升压作用均无影响。两组在血清胆固醇浓度、高密度脂蛋白胆固醇百分比、血糖和胰岛素的血浆浓度、血糖与胰岛素的比值、血清三碘甲状腺原氨酸和甲状腺素浓度以及肌酐清除率方面均未发现显著差异。对6名服用该药物18周的受试者进行BRL 26830A短期给药显示,给药后第二小时能量消耗增加了11.6%,这表明BRL 26830A可能通过产热作用促进体重减轻。BRL 26830A可能是一种治疗肥胖的有效药物。