Current and Potential Drugs for Treatment of Obesity

Bray, George A.

doi:10.1210/er.20.6.805

Cited by 111 publications

(33 citation statements)

References 217 publications

(288 reference statements)

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“…In the present study, the BMI did not depend on whether or not the patients had been treated pharmacologically during the past 4 weeks, probably because the well-documented influence of psychotropic drugs on appetite and weight is variable. Tricyclic antidepressants, for example, increase weight [6, 7], whereas serotonin reuptake inhibitors either have no major effect [7]or even transiently decrease weight [10]. Some antipsychotic drugs such as butyrophenones have little effect, whereas others such as clozapine and olanzapine induce prominent weight gain [8, 9].…”

Section: Discussionmentioning

confidence: 99%

“…A drug-induced reduction of leptin levels has not been reported so far. However, although paroxetine in a small patient sample did neither affect the BMI nor the plasma levels of leptin [7], it cannot be excluded that other SSRIs which reportedly can induce weight loss [10]also decrease leptin levels.…”

Section: Discussionmentioning

confidence: 99%

“…For example, tricyclic antidepressants [6, 7], lithium [6]and some atypical antipsychotic drugs [8]induce weight gain, whereas other antipsychotics have no effect [8, 9], and antidepressants inhibiting the reuptake of serotonin might even induce a transient weight loss [10]. …”

Section: Introductionmentioning

confidence: 99%

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Low Leptin Levels but Norma Body Mass Indices in Patients with Depression or Schizophrenia

et al. 2001

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Appetite, food intake and weight are frequently altered in psychiatric disorders such as major depression and schizophrenia. The few studies investigating weight and the body mass index (BMI) have yielded variable results. Leptin, a fat cell-derived hormone signalling to the brain the size of the adipose tissue, plays a pivotal role in the regulation of weight and food intake. Moreover, leptin is involved in the control of other behaviors and in brain development. There is almost no information about the amounts of circulating leptin in major depression or schizophrenia. We investigated the BMI and plasma leptin levels in patients with major depression (n = 62), schizophrenia (n = 42), and in healthy controls (n = 64). Mean BMIs did not differ between groups. However, leptin levels were significantly lower in both patient groups compared to healthy controls. Moreover, patients suffering from schizophrenia showed significantly lower leptin levels than depressed patients. Decreased leptin levels were independent of psychotropic medication. We conclude that depression and schizophrenia go along with decreased systemic leptin concentrations that cannot be explained by medication or an altered BMI. Hence, leptin might play an important pathophysiological role in these psychiatric disorders that deserves further scientific attention.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Low Leptin Levels but Norma Body Mass Indices in Patients with Depression or Schizophrenia

et al. 2001

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“…The present findings reveal for the first time that the synthetic lipolytic domain is capable of reducing body weight gain in obese Zucker rats through the modulation of lipid metabolism when administered orally. This study demonstrates the potential of developing the synthetic analogues of the lipolytic domain of hGH for obesity therapy, as the current development of new drugs for treatment of obesity seems focussing on those compounds that alter metabolism or increase energy expenditure [29]. …”

Section: Discussionmentioning

confidence: 99%

Metabolic Studies of a Synthetic Lipolytic Domain (AOD9604) of Human Growth Hormone

Sun²,

Sharma³

et al. 2000

Horm Res Paediatr

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A synthetic analogue (AOD9604) of the lipolytic domain of human growth hormone (hGH) has been studied for its metabolic actions in obese Zucker rats. Daily treatment with an oral dose of AOD9604 of 500 µg/kg body weight for 19 days reduced over 50% (15.8 ± 0.6 vs. 35.6 ± 0.8 g) body weight gain of the animals in comparison with the control. The adipose tissues of the AOD9604–treated animals were found to have an increase in lipolytic activity. In contrast to chronic treatment with intact hGH, chronic treatment with AOD9604 showed no adverse effect on insulin sensitivity of the animals, as demonstrated with euglycemic clamp techniques. The results in the present study suggest that the analogue of the hGH lipolytic domain may have the potential to be developed into an orally usable and safe therapeutic agent for obesity.

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“…However drugs in clinical use for treatment of obesity have modest longterm weight-loss benefits (Bray and Greenway, 1999). Antihyperglycemic drugs such as thiazolidinediones have adverse effects such as edema and weight gain, which have limited the development of full agonists to PPARc.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and docking studies of telmisartan analogs for the treatment of metabolic syndrome

et al. 2009

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In our early studies, telmisartan was found to be a moderate peroxisome proliferator-activated receptor (PPAR) gamma activator in the human PPARc-GAL-4 cell-based transactivation assay. Thus, novel analogs of telmisartan were designed, synthesized, and evaluated in the AT 1 receptor binding assay and PPAR gamma transactivation assay. A total of 11 compounds were designed based on docking in both AT 1 receptor model and PPAR gamma active pocket and synthesized. Introduction of an additional acidic group at the para position of the distal phenyl ring of telmisartan decreased affinity towards AT 1 receptor and PPARc activity. In the present study, the molecule with best results was MT003 with weak PPARc activity (8% of maximum PPARc activation achieved by full agonist rosiglitazone at 10 lM) and good binding affinity (K i = 650 ± 139 nM) towards the MEDICINAL CHEMISTRY RESEARCHAT 1 receptor. Docking of MT003 into AT 1 receptor model and PPAR gamma showed very similar interactions with the receptors as AT 1 antagonist telmisartan and PPAR gamma agonist rosiglitazone.

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Current and Potential Drugs for Treatment of Obesity

Cited by 111 publications

References 217 publications

Low Leptin Levels but Norma Body Mass Indices in Patients with Depression or Schizophrenia

Low Leptin Levels but Norma Body Mass Indices in Patients with Depression or Schizophrenia

Metabolic Studies of a Synthetic Lipolytic Domain (AOD9604) of Human Growth Hormone

Design, synthesis, and docking studies of telmisartan analogs for the treatment of metabolic syndrome

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