van Baak Marleen A, Hul Gabby B J, Toubro Søren, Astrup Arne, Gottesdiener Keith M, DeSmet Marina, Saris Wim H M
Nutrition and Toxicology Research Institute (NUTRIM), Department of Human Biology, Maastricht University, The Netherlands.
Clin Pharmacol Ther. 2002 Apr;71(4):272-9. doi: 10.1067/mcp.2002.122527.
Our objective was to investigate the thermogenic efficacy of single oral doses of the novel beta(3)-adrenergic receptor agonist L-796568 [(R )-N -[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]-phenyl]-4-[4-[4-(trifluoromethyl)phenyl]thiazol-2-yl]-benzenesulfonamide, dihydrochloride] in humans.
Twelve healthy overweight to obese men participated in this 2-center, 3-period, randomized, placebo-controlled, crossover trial. In each period subjects received 250 mg L-796568, 1000 mg L-796568, or placebo. Energy expenditure and respiratory quotient were determined by indirect calorimetry; blood samples were taken; and ear temperature, heart rate, and blood pressure were measured at baseline and during the 4-hour period after administration.
Energy expenditure increased significantly after the 1000-mg dose (about 8%) and this was accompanied by an increase in plasma glycerol and free fatty acid concentrations. Systolic blood pressure also increased significantly. No changes in heart rate, diastolic blood pressure, ear temperature, plasma catecholamine, potassium, or leptin were found.
Single-dose administration of 1000 mg of the novel beta(3)-adrenergic receptor agonist L-796568 increased lipolysis and energy expenditure in overweight men. This is the first study to show such an effect of beta(3)-adrenergic receptor agonists in humans without significant evidence for beta(2)-adrenergic receptor involvement.
我们的目的是研究新型β(3)-肾上腺素能受体激动剂L-796568[（R）-N-[4-[2-[[2-羟基-2-(3-吡啶基)乙基]氨基]乙基]-苯基]-4-[4-[4-(三氟甲基)苯基]噻唑-2-基]-苯磺酰胺，二盐酸盐]单次口服剂量对人体的产热功效。
12名健康的超重至肥胖男性参与了这项2中心、3阶段、随机、安慰剂对照、交叉试验。在每个阶段，受试者分别接受250mg L-796568、1000mg L-796568或安慰剂。通过间接测热法测定能量消耗和呼吸商；采集血样；并在基线及给药后4小时内测量耳温、心率和血压。
1000mg剂量后能量消耗显著增加（约8%），同时血浆甘油和游离脂肪酸浓度升高。收缩压也显著升高。未发现心率、舒张压、耳温、血浆儿茶酚胺、钾或瘦素发生变化。
单次给予1000mg新型β(3)-肾上腺素能受体激动剂L-796568可增加超重男性的脂肪分解和能量消耗。这是第一项显示β(3)-肾上腺素能受体激动剂在人体中有这种作用且无明显证据表明β(2)-肾上腺素能受体参与的研究。
