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- Title
Effects of the two β<sub>3</sub>-agonists, ZD7114 and ZD2079 on 24 hour energy expenditure and respiratory quotient in obese subjects.
- Authors
Buemann, B; Toubro, S; Astrup, A
- Abstract
OBJECTIVE: To analyze the effect of two different β[sub 3]-adrenoceptor agonists, ZD7114 and ZD2079 on 24h energy expenditure (EE) and substrate oxidations in obese weight-stable subjects. DESIGN: Measurements of 24 h EE in a respiration chamber, before and after 14 days of treatment with one of the two β[sub 3]-agonists or placebo during weight maintenance. SUBJECTS: ZD7114 study: 7 male and 15 female subjects, body mass index (BMI) 28-39 kg/m², age 27-64 y; ZD2079 study: 10 male and 7 female subjects, BMI 27-39 kg/m², age 31-60 y. MEASUREMENTS: EE was measured by indirect calorimetry, spontaneous physical activity (SPA) assessed by microwave radar, and 24 h heart rate was registered by telemetry. Serum potassium was measured to test for possible β[sub 2]-adrenoceptor activity. RESULTS: No effects of ZD7114 were found on tested parameters whereas there was a trend for a stimulatory effect of ZD2079 on 24 h EE (day 14-pretreatment; ZD2079 vs placebo: 0.4±1.1 vs -2.0±0.4%, P=0.06) and on SPA (day 14pretreatment; ZD2079 vs placebo: 3.4±4.5 vs -7.7±2.7%, P=0.05). However, average 24 h heart rate decreased from 77.5±3.2 to 73.8±2.6min[sup -1] from pre-treatment to day 14 with placebo but remained the same with ZD2079 (P=0.03). The latter suggests some β[sub 1]-adrenoceptor activity of the compound. CONCLUSION: The lack of thermogenic response with ZD7114 and the very small and questionable response with ZD2079 probably demonstrate a lack of consistency between species in the responsiveness to β[sub 3]-stimulation or a diversity in structure of the β[sub 3] receptor since both compounds have proven markedly selective thermogenic β[sub 3]properties in rodents.
- Subjects
BETA adrenoceptors; OBESITY
- Publication
International Journal of Obesity & Related Metabolic Disorders, 2000, Vol 24, Issue 12, p1553
- ISSN
0307-0565
- Publication type
Article
- DOI
10.1038/sj.ijo.0801452