Antiobesity and Antidiabetic β‐agonists: Lessons Learned and Questions to be Answered

Yen, Terence T.

doi:10.1002/j.1550-8528.1994.tb00095.x

Cited by 16 publications

(12 citation statements)

References 56 publications

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“…Unfortunately, the dramatic effect of b 3 agonists in rodents was not con®rmed in humans, probably because of the much smaller amount of such atypical receptors in the adipose tissue of the latter species. 27,28 Nevertheless, some observations support the idea that a selective b 3 -adrenoceptor agonist could induce the appearance of thermogenically active brown adipose tissue in human adults. 23 Whatsoever, the role of b 3 -receptor in human obesity remains unclear 29 and further studies are still needed to assess the potential clinical ef®cacy of b 3 -adrenoceptor agonists in human obesity and type 2 diabetes.…”

Section: 25mentioning

confidence: 88%

Pharmacological treatment of obesity: present status

Scheen

Lefèbvre

1999

Int J Obes

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OBJECTIVE: Obesity poses a serious health hazard and its treatment is often disappointing. This review describes the present status of pharmacological treatment of obesity in man. DESIGN: Obesity treatment may include drugs that reduce food intake, drugs that increase energy expenditure and drugs that affect nutrient partitioning or metabolism. The mode of action, ef®cacy and safety of each approach will be brie¯y discussed. RESULTS: All of the pharmacological possibilities have potential activities, but also serious limitations. While current anti-obesity pharmacotherapy essentially uses centrally-acting anorectic drugs, severe side-effects (more particularly pulmonary hypertension and valvular heart disease) have been reported, leading to the withdrawal of licensed fen¯uramine and d-fen¯uramine. New approaches have been recently proposed, such as sibutramine, an amine reuptake inhibitor which decreases food intake, and orlistat, an intestinal lipase inhibitor which decreases fat absorption.Obesity is a chronic disease and should be treated as such with reasonable expectations. Large-scale one-year placebo-controlled studies demonstrated that d-fen¯uramine, sibutramine and orlistat signi®cantly increased body weight loss by an average of 2 ± 4 kg when compared to placebo and, more interestingly, multiplied by 2 ± 3 the number of patients who succeeded in obtaining and maintaining a reduction of more than 10% of initial body weight. Interestingly, some of these compounds may also exert favourable effects on other vascular risk factors, independently of weight loss. CONCLUSIONS: Even if all anti-obesity pharmacological approaches can be helpful, they also have important limitations so that other strategies including either combined therapies or new drugs (peptides) are currently under investigation.

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Section: 25mentioning

confidence: 88%

Pharmacological treatment of obesity: present status

Scheen

Lefèbvre

1999

Int J Obes

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“…In addition to actions at the enzyme level, these compounds also stimulate the transcription of m-RNA for Glut-4 (7) and the mitochondria1 membrane uncoupling protein (15). The fact that rat p,-selective agonists are able to maintain antiobesity activity in experimental animals suggests that PI-and P,-agonist activities are not necessary (28,50).…”

Section: Preclinicalmentioning

confidence: 99%

“…Some of the antiobesity and antidiabetic data, especially those fiomtheBRLseries, havebeenreviewed (5,12,43). Inaddition, amore comprehensive review onthe metabolic activities of pagonists appeared recently (50). The nutrient partitioning activity of these compounds has also beenreviewed in several publications (2,49,51).…”

mentioning

confidence: 99%

β‐Agonists as Antiobesity, Antidiabetic and Nutrient Partitioning Agents

Yen

1995

Obesity Research

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YEN,TERENCE T. P-agonists as antiobesity, antidiabetic and nutrient partitioning agents. Obes Res. 1995;3(SupplIn the past decade, the antiobesity, antidiabetic andnutrient partitioning activities of P-agonists have been extensively studied. Thedata generatedfromthesecompounds inexperimentalandfarmanimals haveconvincingly provedthat body fat content andbodyweightcan bemoditiedto somedegreeby a metabolic agent without decreasing food consumption. Marginal antiobesity and antidiabetic activities in humans have been demonstratedwith afew mixed P-agonists under certain conditions, but their utility is limited by side effects. The concept of a P,-receptor rose from the study of these compounds and has beenverified by the cloning and expression of this receptor from several species. Rat p,-selective agonistshaveso far shownno antiobesityefficacyinhumans. The resolution of several issues is critical for the discovery and development of efficacious antiobesity and antidiabetic agents with minimum side effects. Ultimately, the further investigationof these P-agonists and P-receptors shouldlead to a better understanding of the relationship between energy metabolism and feeding behavior.4):5318-5368.

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“…This drug stimulates oxygen consumption in the genetically obese leptindeficient ob/ob mouse and causes weight loss and a decrease in body fat, but conserves or increases lean body mass (974). The drug also stimulates lactate production and inhibits glycogen synthesis in skeletal muscle from rats.…”

Section: ␤ 3 -Adrenergic Agonistsmentioning

confidence: 99%

“…Because the ␤ 3 -adrenergic receptor mediated the thermogenic response to NE, it was an ideal candidate for pharmaceutical development of agonists (974,975). The first generation of phenethanolamine agonists was developed against the rat receptor using lipolysis in white adipose tissue as an assay.…”

Section: ␤ 3 -Adrenergic Agonistsmentioning

confidence: 99%