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Chemical Compound Review

Butramin     1-[1-(4- chlorophenyl)cyclobutyl]- N,N,3...

Synonyms: Reductil, Medaria, Meridia, Sibutramina, sibutramine, ...
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Disease relevance of C07247


Psychiatry related information on C07247


High impact information on C07247

  • OBJECTIVE: To examine whether increased weight loss in obese adolescents is induced when sibutramine is added to a family-based, behavioral weight control program [8].
  • Behavior therapy and sibutramine for the treatment of adolescent obesity: a randomized controlled trial [8].
  • RESULTS: In intention-to-treat analysis at month 6, participants in the BT and sibutramine group lost a mean (SD) of 7.8 kg (6.3 kg) and had an 8.5% (6.8%) reduction in BMI, which was significantly more than weight loss of 3.2 kg (6.1 kg) and reduction in BMI of 4.0% (5.4%) in the BT and placebo group [8].
  • 20 (3%) patients were withdrawn because of increases in blood pressure; in the sibutramine group, systolic blood pressure rose from baseline to 2 years by 0.1 mm Hg (SD 12.9), diastolic blood pressure by 2.3 mm Hg (9.4), and pulse rate by 4.1 beats/min (11.9) [13].
  • HDL cholesterol concentrations rose substantially in the second year: overall increases were 20.7% (sibutramine) and 11.7% (placebo, p<0.001) [13].

Chemical compound and disease context of C07247


Biological context of C07247


Anatomical context of C07247

  • RESEARCH METHODS AND PROCEDURES: A total of 15 premenopausal, African American women (age, 29 +/- 5 years; body fat, 38 +/- 7%) completed a randomized, double-blind cross-over design with a 30-mg ingestion of sibutramine or a placebo [22].
  • Absence of cardiac valve dysfunction in obese patients treated with sibutramine [23].
  • In vitro, sibutramine blocked [(3)H]-dopamine uptake into striatal synaptosomes, with an IC(50) value of 3.8 microM [24].
  • RX821002 also reduced the latency of sibutramine to reach its maximum effect in the cortex, but not in the hypothalamus [25].
  • The parallel findings of a high level of brown adipocyte activation and low parenchymal noradrenergic innervation are discussed and a possible direct effect of sibutramine and/or its active metabolites on peripheral BAT sympathetic nerve terminals is hypothesized [26].

Associations of C07247 with other chemical compounds


Gene context of C07247

  • DISCUSSION: The homozygosity/heterozygosity of the PNMT gene was highly predictive of significant weight loss with sibutramine during the first 3 months, which highlights the need for specific pharmacotherapy [31].
  • Sibutramine treatment increased sympathetic activity, attenuated the increased ARC NPY, and decreased POMC mRNA levels induced by energy restriction in RV rats [32].
  • If also observed in humans, the pharmacological profile of MC4-R agonists would not offer a significant therapeutic advantage over currently used appetite suppressants such as sibutramine [33].
  • Sibutramine improves fat distribution and insulin resistance, and increases serum adiponectin levels in Korean obese nondiabetic premenopausal women [34].
  • Prediction of successful weight reduction under sibutramine therapy through genotyping of the G-protein beta3 subunit gene (GNB3) C825T polymorphism [35].

Analytical, diagnostic and therapeutic context of C07247

  • METHODS: Eight European centres recruited 605 obese patients (body-mass index 30-45 kg/m2) for a 6-month period of weight loss with sibutramine (10 mg/day) and an individualised 600 kcal/day deficit programme based on measured resting metabolic rates [13].
  • EE was measured by indirect calorimetry before and for 5.5 h after sibutramine or placebo administration with or without a 2.1-MJ breakfast [21].
  • RESEARCH DESIGN AND METHODS: Controlled clinical trials assessing the effect sizes of sibutramine on weight loss effects on glycemia in obese subjects with type 2 diabetes were identified and reviewed using the Cochrane Library, Medline, EMBASE, and a manual search [36].
  • In clinical trials, once-daily sibutramine was administered at dosages of < or = 30 mg for < or = 24 weeks and 10 or 15 mg for 1 year in conjunction with reduced calorie intake, increased daily exercise and advice on eating behaviour [37].
  • Drug therapy for weight loss is available (at present, sibutramine is the only approved appetite suppressant in the United States); however, for most patients already being treated with a psychotropic agent, the risks (such as drug interactions, adverse events, compliance problems) of adding an antiobesity agent probably outweigh the benefits [38].


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  2. Measuring the effect of sibutramine for weight loss. Ransom, T., Ur, E. JAMA (2002) [Pubmed]
  3. A randomized, double-blind, placebo-controlled study of sibutramine in the treatment of binge-eating disorder. Appolinario, J.C., Bacaltchuk, J., Sichieri, R., Claudino, A.M., Godoy-Matos, A., Morgan, C., Zanella, M.T., Coutinho, W. Arch. Gen. Psychiatry (2003) [Pubmed]
  4. The cost-effectiveness of sibutramine in non-diabetic obese patients: evidence from four Western countries. Ara, R., Brennan, A. Obes. Rev (2007) [Pubmed]
  5. Sympathetic vasomotor tone determines blood pressure response to long-term sibutramine treatment. Heusser, K., Engeli, S., Tank, J., Diedrich, A., Wiesner, S., Janke, J., Luft, F.C., Jordan, J. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  6. Efficacy of sibutramine for the treatment of binge eating disorder: a randomized multicenter placebo-controlled double-blind study. Wilfley, D.E., Crow, S.J., Hudson, J.I., Mitchell, J.E., Berkowitz, R.I., Blakesley, V., Walsh, B.T. Am. J. Psychiatry (2008) [Pubmed]
  7. Weight loss and body fat reduction under sibutramine therapy in obesity with the C825T polymorphism in the GNB3 gene. Hsiao, D.J., Wu, L.S., Huang, S.Y., Lin, E. Pharmacogenet. Genomics (2009) [Pubmed]
  8. Behavior therapy and sibutramine for the treatment of adolescent obesity: a randomized controlled trial. Berkowitz, R.I., Wadden, T.A., Tershakovec, A.M., Cronquist, J.L. JAMA (2003) [Pubmed]
  9. A double-blind, placebo-controlled trial of sibutramine for olanzapine-associated weight gain. Henderson, D.C., Copeland, P.M., Daley, T.B., Borba, C.P., Cather, C., Nguyen, D.D., Louie, P.M., Evins, A.E., Freudenreich, O., Hayden, D., Goff, D.C. The American journal of psychiatry. (2005) [Pubmed]
  10. Sibutramine and panic attacks. Binkley, K., Knowles, S.R. The American journal of psychiatry. (2002) [Pubmed]
  11. Leisure-time activity is an important determinant of long-term weight maintenance after weight loss in the Sibutramine Trial on Obesity Reduction and Maintenance (STORM trial). van Baak, M.A., van Mil, E., Astrup, A.V., Finer, N., Van Gaal, L.F., Hilsted, J., Kopelman, P.G., Rössner, S., James, W.P., Saris, W.H. Am. J. Clin. Nutr. (2003) [Pubmed]
  12. One-year outcome of a combination of weight loss therapies for subjects with type 2 diabetes: a randomized trial. Redmon, J.B., Raatz, S.K., Reck, K.P., Swanson, J.E., Kwong, C.A., Fan, Q., Thomas, W., Bantle, J.P. Diabetes Care (2003) [Pubmed]
  13. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. James, W.P., Astrup, A., Finer, N., Hilsted, J., Kopelman, P., Rössner, S., Saris, W.H., Van Gaal, L.F. Lancet (2000) [Pubmed]
  14. Long-term weight loss with sibutramine: a randomized controlled trial. Wirth, A., Krause, J. JAMA (2001) [Pubmed]
  15. The efficacy and safety of sibutramine for weight loss: a systematic review. Arterburn, D.E., Crane, P.K., Veenstra, D.L. Arch. Intern. Med. (2004) [Pubmed]
  16. Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects. Heusser, K., Tank, J., Diedrich, A., Engeli, S., Klaua, S., Krüger, N., Strauss, A., Stoffels, G., Luft, F.C., Jordan, J. Clin. Pharmacol. Ther. (2006) [Pubmed]
  17. Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Kim, S.H., Lee, Y.M., Jee, S.H., Nam, C.M. Obes. Res. (2003) [Pubmed]
  18. A comparison of sibutramine and dexfenfluramine in the treatment of obesity. Hanotin, C., Thomas, F., Jones, S.P., Leutenegger, E., Drouin, P. Obes. Res. (1998) [Pubmed]
  19. Mapping striate and extrastriate visual areas in human cerebral cortex. DeYoe, E.A., Carman, G.J., Bandettini, P., Glickman, S., Wieser, J., Cox, R., Miller, D., Neitz, J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  20. Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial. McMahon, F.G., Fujioka, K., Singh, B.N., Mendel, C.M., Rowe, E., Rolston, K., Johnson, F., Mooradian, A.D. Arch. Intern. Med. (2000) [Pubmed]
  21. Thermogenic effects of sibutramine in humans. Hansen, D.L., Toubro, S., Stock, M.J., Macdonald, I.A., Astrup, A. Am. J. Clin. Nutr. (1998) [Pubmed]
  22. Influence of sibutramine on energy expenditure in African American women. Starling, R.D., Liu, X., Sullivan, D.H. Obes. Res. (2001) [Pubmed]
  23. Absence of cardiac valve dysfunction in obese patients treated with sibutramine. Bach, D.S., Rissanen, A.M., Mendel, C.M., Shepherd, G., Weinstein, S.P., Kelly, F., Seaton, T.B., Patel, B., Pekkarinen, T.A., Armstrong, W.F. Obes. Res. (1999) [Pubmed]
  24. Sibutramine, a serotonin uptake inhibitor, increases dopamine concentrations in rat striatal and hypothalamic extracellular fluid. Balcioglu, A., Wurtman, R.J. Neuropharmacology (2000) [Pubmed]
  25. Modulation of sibutramine-induced increases in extracellular noradrenaline concentration in rat frontal cortex and hypothalamus by alpha2-adrenoceptors. Wortley, K.E., Heal, D.J., Stanford, S.C. Br. J. Pharmacol. (1999) [Pubmed]
  26. Sibutramine-dependent brown fat activation in rats: an immunohistochemical study. Giordano, A., Centemeri, C., Zingaretti, M.C., Cinti, S. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  27. Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes mellitus: a meta-analysis. Norris, S.L., Zhang, X., Avenell, A., Gregg, E., Schmid, C.H., Kim, C., Lau, J. Arch. Intern. Med. (2004) [Pubmed]
  28. A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin. McNulty, S.J., Ur, E., Williams, G. Diabetes Care (2003) [Pubmed]
  29. Serotonergic drugs : effects on appetite expression and use for the treatment of obesity. Halford, J.C., Harrold, J.A., Boyland, E.J., Lawton, C.L., Blundell, J.E. Drugs (2007) [Pubmed]
  30. The contribution of metabolites to the rapid and potent down-regulation of rat cortical beta-adrenoceptors by the putative antidepressant sibutramine hydrochloride. Luscombe, G.P., Hopcroft, R.H., Thomas, P.C., Buckett, W.R. Neuropharmacology (1989) [Pubmed]
  31. Phenylethanolamine N-methyltransferase G-148A genetic variant and weight loss in obese women. Peters, W.R., MacMurry, J.P., Walker, J., Giese, R.J., Comings, D.E. Obes. Res. (2003) [Pubmed]
  32. Sibutramine alters the central mechanisms regulating the defended body weight in diet-induced obese rats. Levin, B.E., Dunn-Meynell, A.A. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2000) [Pubmed]
  33. Cardiovascular responses to melanocortin 4-receptor stimulation in conscious unrestrained normotensive rats. Nordheim, U., Nicholson, J.R., Dokladny, K., Dunant, P., Hofbauer, K.G. Peptides (2006) [Pubmed]
  34. Sibutramine improves fat distribution and insulin resistance, and increases serum adiponectin levels in Korean obese nondiabetic premenopausal women. Kim, D.M., Yoon, S.J., Ahn, C.W., Cha, B.S., Lim, S.K., Kim, K.R., Lee, H.C., Huh, K.B. Diabetes Res. Clin. Pract. (2004) [Pubmed]
  35. Prediction of successful weight reduction under sibutramine therapy through genotyping of the G-protein beta3 subunit gene (GNB3) C825T polymorphism. Hauner, H., Meier, M., Jöckel, K.H., Frey, U.H., Siffert, W. Pharmacogenetics (2003) [Pubmed]
  36. Effect of sibutramine on weight management and metabolic control in type 2 diabetes: a meta-analysis of clinical studies. Vettor, R., Serra, R., Fabris, R., Pagano, C., Federspil, G. Diabetes Care (2005) [Pubmed]
  37. Sibutramine. A review of its contribution to the management of obesity. McNeely, W., Goa, K.L. Drugs (1998) [Pubmed]
  38. Nonpharmacologic and pharmacologic management of weight gain. Greenberg, I., Chan, S., Blackburn, G.L. The Journal of clinical psychiatry. (1999) [Pubmed]
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