Effects of the two beta(3)-agonists, ZD7114 and ZD2079 on 24 hour energy expenditure and respiratory quotient in obese subjects

OBJECTIVE: To analyze the effect of two different B-2-adrenoceptor agonists , ZD7114 and ZD2079 on 24 h energy expenditure (EE) and substrate oxidation s 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 B-3-agonists or placebo during wei ght maintenance. SUBJECTS: ZD7114 study: 7 male and 15 female subjects, body mass index (BMI ) 28-39 kg/m(2), age 27-64 y; ZD2079 study: 10 male and 7 female subjects, BMI 27-39 kg/m(2), 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 regist ered by telemetry. Serum potassium was measured to test for possible beta ( 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-pretreat ment; ZD2079 vs placebo: 0.4+/-1.1 vs - 2.0+/-0.4%, P= 0.06) and on SPA (da y 14-pretreatment; 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 (-1) from pre-treatment to day 14 with placebo but remained the same with Z D2079 (P= 0.03). The latter suggests some beta (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 B-3-stimulat ion or a diversity in structure of the beta (3) receptor since both compoun ds have proven markedly selective thermogenic B-3 properties in rodents.