brl-26830a and Weight-Loss

BRL 26830A is a beta-adrenoceptor agonist drug that shows a high degree of selectivity for thermogenesis and has potential as an antiobesity agent. We undertook a double-blind trial in 40 obese subjects who received either BRL 26830A or placebo for 18 wk. All were prescribed a 3.35 MJ (800 kcal) diet. Weight loss was 15.4 +/- 6.6 (SD) kg on BRL 26830A compared with 10.0 +/- 5.9 kg on placebo (P less than 0.02). The relative weight losses were 0.93% and 0.61%/wk, respectively. Urinary nitrogen excretion was similar in both groups and skinfold measurements indicated a 4-kg difference in fat lost, suggesting that weight loss was mainly from adipose tissue. Psychological assessments showed that BRL 26830A had no adverse effect on mood and no effect on hunger or satiety. Tremor was experienced by 12 of 16 treated subjects who completed the study. It was generally rated as mild, occurred 1 h after dosing, and tended to diminish with time on treatment. Subsequent analysis of the tremor suggested that it is an exaggeration of physiological tremor mediated through skeletal muscle beta 2 adrenoceptors.

Topics: Adrenergic beta-Agonists; Body Temperature Regulation; Double-Blind Method; Ethanolamines; Humans; Obesity; Weight Loss

BRL 26830A is a beta-adrenoceptor agonist drug that shows a high degree of selectivity for thermogenesis and has potential as an antiobesity agent. We undertook a double-blind trial in 40 obese subjects who received either BRL 26830A or placebo for 18 wk. All were prescribed a 3.35 MJ (800 kcal) diet. Weight loss was 15.4 +/- 6.6 (SD) kg on BRL 26830A compared with 10.0 +/- 5.9 kg on placebo (P less than 0.02). The relative weight losses were 0.93% and 0.61%/wk, respectively. Urinary nitrogen excretion was similar in both groups and skinfold measurements indicated a 4-kg difference in fat lost, suggesting that weight loss was mainly from adipose tissue. Psychological assessments showed that BRL 26830A had no adverse effect on mood and no effect on hunger or satiety. Tremor was experienced by 12 of 16 treated subjects who completed the study. It was generally rated as mild, occurred 1 h after dosing, and tended to diminish with time on treatment. Subsequent analysis of the tremor suggested that it is an exaggeration of physiological tremor mediated through skeletal muscle beta 2 adrenoceptors.

Topics: Adrenergic beta-Agonists; Body Temperature Regulation; Double-Blind Method; Ethanolamines; Humans; Obesity; Weight Loss

Psychological aspects of dieting, including hunger and satiety sensations were explored in obese subjects during a placebo-controlled trial of the weight reducing potential of BRL 26830A, a thermogenic beta-3-agonist drug. Successful weight loss was associated with a reduction in the severity of reported depression. The initial degree of emotional disturbance and level of learned resourcefulness appeared to influence the subsequent weight lost. Subjects described few specific hunger and satiety sensations and these sensations did not generally alter during the trial. BRL 26830A, which promoted weight loss, did not significantly influence hunger and satiety sensations and was not associated with emotional disturbances during dieting. With BRL 26830A there was a reduction in the reported somatic symptoms of anxiety which was not apparent on placebo. These results suggest that the subjects' initial psychological state influences outcome when dieting and also that dynamic changes in psychological parameters occur with successful weight loss. Further, BRL 26830A had no effect on appetite and no adverse influence on the psychological functions tested during this study.

Topics: Adrenergic beta-Agonists; Adult; Affect; Analysis of Variance; Diet, Reducing; Double-Blind Method; Ethanolamines; Female; Humans; Hunger; Male; Middle Aged; Obesity; Psychological Tests; Satiation; Weight Loss

We compared the effects of hypothalamic obesity induced by neonatal monosodium glutamate (MSG) treatment between spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Newborn WKY and SHR were injected intraperitoneally with 4 mg/kg body weight of MSG daily for 5 days. At 6 months of age, the obesity of SHR was more advanced than that of WKY, but at 14 months of age the severity of obesity was similar between the two strains. Hypertriglyceridemia was enhanced in MSG-treated SHR as compared with MSG-treated WKY. Systolic blood pressure measured by the tail-cuff method was consistently lower in MSG-treated SHR than in control SHR, whereas blood pressure was not affected by neonatal MSG treatment in WKY. Food restriction reduced body weight more in control SHR than in control WKY, with the former also showing enhanced ketogenesis. Neonatal MSG treatment abolished the accelerated reduction of body weight in SHR. Serum leptin concentration was markedly increased in MSG-treated obese rats, though no differences were seen between WKY and SHR in the control or MSG-treated groups. Serum leptin was closely correlated with both Lee obese index and mesenteric fat weight over the strain. Blood flow in interscapular brown adipose tissue (BAT) measured by Laser Doppler flowmetry was significantly increased in response to beta3-adrenoceptor agonist BRL26830A in both the control and MSG-treated rats. However, the response of blood flow was not affected by MSG treatment or strain difference. The present study demonstrated some strain differences in response to neonatal MSG treatment between WKY and SHR. These differences could not be explained by the difference in serum leptin level or beta3-adrenergic reactivity in BAT.

Topics: Adipose Tissue, Brown; Adrenergic beta-3 Receptor Agonists; Adrenergic beta-Agonists; Animals; Blood Pressure; Disease Models, Animal; Energy Intake; Ethanolamines; Female; Food Additives; Hypertension; Leptin; Male; Obesity; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Regional Blood Flow; Sodium Glutamate; Weight Loss