POSSIBLE PERIPHERAL LIPOLYTIC EFFECT OF CLOBENZOREX HYDROCHLORIDE IN PATIENTS WITH OBESITY
Keywords:
clobenzorex hydrochloride, drug treatment, obesity
Abstract
Introduction: It is well known that clobenzorex hydrochloride is an amine that inhibits appetite by its sympathomimetic action on the lateral hypothalamus. However, it has been reported that this drug also has a peripheral lipolytic effect, which has not been studied sufficiently. The aim of this study was to evaluate such lipolytic action in obese patients.
Methods: A controlled clinical trial was conducted with male and female patients having class I and II obesity and an age range of 30-60 years (n=33). Patients were randomized into two groups: the experimental group (n=16) received a single oral dose of 90 mg clobenzorex, and the control group (n=17) a placebo. Blood samples were taken at 0, 60, 120, 180 and 240 min post-administration to determine serum levels of free fatty acids (FFAs), glycerol, glucose, triglycerides, HDLcholesterol and LDL-cholesterol. The atherogenic index (AI) was calculated.
Results: Over the time of the study (0-240 min), the experimental group showed an increase in HDL-cholesterol (from 42.0 to 55.6 mg/dl; p=0.01), FFAs (from 0461 to 1009 mMol/l; p=0.01), and glycerol (from 0.123 to 0.170 mMol/lt; p=0.01). There was a significant decrease in AI (from 5.87 to 5.26; p=0.01). The placebo group showed a significant increase only in FFAs (from 0436 to 0824 mMol/lt; p=0.01) and a significant decrease in AI (from 4.51 to 4.05; p=0.01).
Conclusion: These results suggest that clobenzorex hydrochloride has peripheral lipolytic activity, which can be considered as an additional effect, synergistic with its central pharmacological mechanism.
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References
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26. Langin D. Control of fatty acid and glycerol release in adipose tissue lipolysis. C R Biol. 2006;329(8):598-607; discussion 53-5.
27. Lafontan M, Barbe P, Galitzky J, Tavernier G, Langin D, Carpene C, et al. Adrenergic regulation of adipocyte metabolism. Hum Reprod. 1997;12 Suppl 1:6-20.
28. Carmen GY, Victor SM. Signalling mechanisms regulating lipolysis. Cell Signal. 2006;18(4):401-8.
29. Carey GB. Mechanisms regulating adipocyte lipolysis. Adv Exp Med Biol. 1998;441:157-70.
30. Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS. Regulation of lipolysis in adipocytes. Annu Rev Nutr. 2007;27:79-101.
31. Bezaire V, Mairal A, Ribet C, Lefort C, Girousse A, Jocken J, et al. Contribution of adipose triglyceride lipase and hormonesensitive lipase to lipolysis in hMADS
adipocytes. J Biol Chem. 2009;284(27):18282-91.
32. Pinter EJ, Patee CJ. Fat-mobilizing action of amphetamine. J Clin Invest. 1968;47(2):394-402.
33. Jocken JW, Blaak EE. Catecholamineinduced lipolysis in adipose tissue and skeletal muscle in obesity. Physiol Behav. 2008;94(2):219-30.
34. Jocken JW, Roepstorff C, Goossens GH, van der Baan P, van Baak M, Saris WH, et al. Hormone-sensitive lipase serine phosphorylation and glycerol exchange
across skeletal muscle in lean and obese subjects: effect of beta-adrenergic stimulation. Diabetes. 2008;57(7):1834-41.
35. Bryant KR, Rothwell NJ, Stock MJ, Wyllie MG. Parasympathethic effects on diet-induced thermogenesis. Eur J Pharmacol. 1983;95(3-4):291-4.
36. Roger P, Pawan GL, Riviere J. [Fat mobilization factors]. Bord Med. 1972;5(15):1851-8.
37. Kozak LP, Anunciado-Koza R. UCP1: its involvement and utility in obesity. Int J Obes (Lond). 2008;32 Suppl 7:S32-8.
38. Kozak LP, Koza RA, Anunciado-Koza R. Brown fat thermogenesis and body weight regulation in mice: relevance to humans. Int J Obes (Lond). 2010;34 Suppl
1:S23-7.
39. Baumeister RG, Richter WO, Riel KA, Schwandt P, Bohmert H. [Regulation of lipolysis--biochemical research on the fat cells of obese patients]. Handchir Mikrochir Plast Chir. 1986;18(3):115-7.
40. Wahrenberg H, Bolinder J, Arner P . Adrenergic regulation of lipolysis in human fat cells during exercise. Eur J Clin Invest. 1991;21(5):534-41.
41. Large V, Reynisdottir S, Langin D, Fredby K, Klannemark M, Holm C, et al. Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. J Lipid Res. 1999;40(11):2059-66.
42. Wallace RB, Colsher PL. Blood lipid distributions in older persons. Prevalence and correlates of hyperlipidemia. Ann Epidemiol. 1992;2(1-2):15-21.
43. Schaefer EJ, Lamon-Fava S, Cohn SD, Schaefer MM, Ordovas JM, Castelli WP, et al. Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study. J Lipid Res. 1994;35(5):779-92.
44. Upadhyay RK. Emerging risk biomarkers in cardiovascular diseases and disorders. J Lipids. 2015;2015:971453
2. Chait LD, Johanson CE. Discriminative stimulus effects of caffeine and benzphetamine in amphetamine-trained volunteers. Psychopharmacology (Berl). 1988;96(3):302-8.
3. Cody JT, Valtier S. Amphetamine, clobenzorex, and 4-hydroxyclobenzorex levels following multidose administration of clobenzorex. J Anal Toxicol. 2001;25(3):158-65.
4. Baden KL, Valtier S, Cody JT. Metabolic production of amphetamine following multidose administration of clobenzorex. J Anal Toxicol. 1999;23(6):511-7.
5. Charbonnier A, Nepveux P, Neuman M. [Effect of a new anorexigenic drug, clobenzorex chlorhydrate on mobilizable lipids in human]. Therapie. 1972;27(5):831-
48.
6. Ahmadian M, Duncan RE, Jaworski K, Sarkadi-Nagy E, Sul HS. Triacylglycerol metabolism in adipose tissue. Future Lipidol. 2007;2(2):229-37.
7. Jaworski K, Sarkadi-Nagy E, Duncan RE, Ahmadian M, Sul HS. Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in adipose tissue. Am
J Physiol Gastrointest Liver Physiol. 2007;293(1):G1-4.
8. Okazaki H, Igarashi M, Nishi M, Tajima M, Sekiya M, Okazaki S, et al. Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol: a potential role in adipocyte lipolysis. Diabetes. 2006;55(7):2091-7.
9. Dolinsky VW, Gilham D, Alam M, Vance DE, Lehner R. Triacylglycerol hydrolase: role in intracellular lipid metabolism. Cell Mol Life Sci. 2004;61(13):1633-51.
10. Fortier M, Wang SP, Mauriege P, Semache M, Mfuma L, Li H, et al. Hormone-sensitive lipase-independent adipocyte lipolysis during beta-adrenergic stimulation, fasting, and dietary fat loading. Am J Physiol Endocrinol Metab. 2004;287(2):E282-8.
11. Ryden M, Jocken J, van Harmelen V, Dicker A, Hoffstedt J, Wiren M, et al. Comparative studies of the role of hormone-sensitive lipase and adipose triglyceride lipase in human fat cell lipolysis. Am J Physiol Endocrinol Metab. 2007;292(6):E1847-55.
12. Dagenais GR, Yi Q, Mann JF, Bosch J, Pogue J, Yusuf S. Prognostic impact of body weight and abdominal obesity in women and men with cardiovascular disease. Am Heart J. 2005;149(1):54-60.
13. Mooradian AD, Haas MJ, Wehmeier KR, Wong NC. Obesity-related changes in high-density lipoprotein metabolism. Obesity (Silver Spring). 2008;16(6):1152-60.
14. Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, et al. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med. 2014;371(25):2383-93.
15. Bhatt A, Rohatgi A. HDL Cholesterol Efflux Capacity: Cardiovascular Risk Factor and Potential Therapeutic Target. Curr Atheroscler Rep. 2016;18(1):2.
16. Garcia-Morales LM, Berber A, Macias-Lara CC, Lucio-Ortiz C, Del-RioNavarro BE, Dorantes-Alvarez LM. Use of sibutramine in obese mexican adolescents: a 6-month, randomized, double-blind, placebo-controlled, parallel-group trial. Clin Ther. 2006;28(5):770-82.
17. Bray GA, Ryan DH, Gordon D, Heidingsfelder S, Cerise F, Wilson K. A double-blind randomized placebocontrolled trial of sibutramine. Obes Res. 1996;4(3):263-70.
18. Valtier S, Cody JT. Metabolic production of amphetamine following administration of clobenzorex. J Forensic Sci. 1999;44(1):17-22.
19. Badimon L, Hernandez Vera R, Vilahur G. Atherothrombotic risk in obesity. Hamostaseologie. 2013;33(4):259- 68.
20. Rothwell NJ, Stock MJ, Wyllie MG. Sympathetic mechanisms in diet-inducedDownloaded from Medico Research Chronicles “Possible peripheral lipolytic effect of Clobenzorex hydrochloride in patients with obesity” Cortés-Moreno Gabriela Y. et al., Med. Res. Chron., 2017, 4 (3), 252-265 Medico Research Chronicles, 2017 264 thermogenesis: modification by ciclazindol and anorectic drugs. Br J Pharmacol. 1981;74(3):539-46.
21. Pawan GL. Effect of fenfluramine on blood-lipids in man. Lancet. 1969;1(7593):498-500.
22. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce
atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
Circulation. 2014;129(25 Suppl 2):S1-45.
23. Kang JG, Park CY, Kang JH, Park YW, Park SW. Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity. Diabetes Obes Metab. 2010;12(10):876-82.
24. Grundy SM. Atherosclerosis imaging and the future of lipid management. Circulation. 2004;110(23):3509-11.
25. Kinosian B, Glick H, Preiss L, Puder KL. Cholesterol and coronary heart disease: predicting risks in men by changes in levels and ratios. J Investig Med. 995;43(5):443-50.
26. Langin D. Control of fatty acid and glycerol release in adipose tissue lipolysis. C R Biol. 2006;329(8):598-607; discussion 53-5.
27. Lafontan M, Barbe P, Galitzky J, Tavernier G, Langin D, Carpene C, et al. Adrenergic regulation of adipocyte metabolism. Hum Reprod. 1997;12 Suppl 1:6-20.
28. Carmen GY, Victor SM. Signalling mechanisms regulating lipolysis. Cell Signal. 2006;18(4):401-8.
29. Carey GB. Mechanisms regulating adipocyte lipolysis. Adv Exp Med Biol. 1998;441:157-70.
30. Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS. Regulation of lipolysis in adipocytes. Annu Rev Nutr. 2007;27:79-101.
31. Bezaire V, Mairal A, Ribet C, Lefort C, Girousse A, Jocken J, et al. Contribution of adipose triglyceride lipase and hormonesensitive lipase to lipolysis in hMADS
adipocytes. J Biol Chem. 2009;284(27):18282-91.
32. Pinter EJ, Patee CJ. Fat-mobilizing action of amphetamine. J Clin Invest. 1968;47(2):394-402.
33. Jocken JW, Blaak EE. Catecholamineinduced lipolysis in adipose tissue and skeletal muscle in obesity. Physiol Behav. 2008;94(2):219-30.
34. Jocken JW, Roepstorff C, Goossens GH, van der Baan P, van Baak M, Saris WH, et al. Hormone-sensitive lipase serine phosphorylation and glycerol exchange
across skeletal muscle in lean and obese subjects: effect of beta-adrenergic stimulation. Diabetes. 2008;57(7):1834-41.
35. Bryant KR, Rothwell NJ, Stock MJ, Wyllie MG. Parasympathethic effects on diet-induced thermogenesis. Eur J Pharmacol. 1983;95(3-4):291-4.
36. Roger P, Pawan GL, Riviere J. [Fat mobilization factors]. Bord Med. 1972;5(15):1851-8.
37. Kozak LP, Anunciado-Koza R. UCP1: its involvement and utility in obesity. Int J Obes (Lond). 2008;32 Suppl 7:S32-8.
38. Kozak LP, Koza RA, Anunciado-Koza R. Brown fat thermogenesis and body weight regulation in mice: relevance to humans. Int J Obes (Lond). 2010;34 Suppl
1:S23-7.
39. Baumeister RG, Richter WO, Riel KA, Schwandt P, Bohmert H. [Regulation of lipolysis--biochemical research on the fat cells of obese patients]. Handchir Mikrochir Plast Chir. 1986;18(3):115-7.
40. Wahrenberg H, Bolinder J, Arner P . Adrenergic regulation of lipolysis in human fat cells during exercise. Eur J Clin Invest. 1991;21(5):534-41.
41. Large V, Reynisdottir S, Langin D, Fredby K, Klannemark M, Holm C, et al. Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. J Lipid Res. 1999;40(11):2059-66.
42. Wallace RB, Colsher PL. Blood lipid distributions in older persons. Prevalence and correlates of hyperlipidemia. Ann Epidemiol. 1992;2(1-2):15-21.
43. Schaefer EJ, Lamon-Fava S, Cohn SD, Schaefer MM, Ordovas JM, Castelli WP, et al. Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study. J Lipid Res. 1994;35(5):779-92.
44. Upadhyay RK. Emerging risk biomarkers in cardiovascular diseases and disorders. J Lipids. 2015;2015:971453
How to Cite
1.
Cortés-Moreno Gabriela Y, Heald-H Adrian, Miliar-García Ángel, Morín-Zaragoza Raúl, Guerrero-Domínguez Rafae, Lara-Padilla Eleazar. POSSIBLE PERIPHERAL LIPOLYTIC EFFECT OF CLOBENZOREX HYDROCHLORIDE IN PATIENTS WITH OBESITY. Med. res. chronicles [Internet]. 1 [cited 2024Apr.19];4(03):252-65. Available from: https://medrech.com/index.php/medrech/article/view/239
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