A Historical Overview Upon the Use of Amphetamine Derivatives in the Treatment of Obesity

  • Ștefana Stăcescu University of Medicine, Pharmacy, Science and Technology of Tîrgu Mureș, Faculty of Pharmacy, Department of Pharmaceutical Chemistry
  • Gabriel Hancu University of Medicine, Pharmacy, Science and Technology of Tîrgu Mureș, Faculty of Pharmacy, Department of Pharmaceutical Chemistry
  • Denisa Podar University of Medicine, Pharmacy, Science and Technology of Tîrgu Mureș, Faculty of Pharmacy, Department of Pharmaceutical Chemistry
  • Ștefania Todea Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy from Tîrgu Mureș, Tîrgu Mureș, Romania
  • Amelia Tero-Vescan University of Medicine, Pharmacy, Science and Technology of Tîrgu Mureș, Faculty of Pharmacy, Department of Biochemistry
Keywords: Amphetamines, Obesity, Pharmacotherapy


Relatively few medications are available for the management of obesity and all are indicated as adjuncts to increased physical activity, caloric restriction and lifestyle modification. Among different weight-loss drugs, the most intriguing and controversial class is the one of anorexic amphetamines, due to their high efficiency but also relevant side-effects. Several previously approved anorexic amphetamines like fenfluramine, phenylpropanolamine, phenmetrazine and sibutramine have been withdrawn from the market due to unanticipated adverse effects. Nowadays only four amphetamine derivatives are approved for short-term treatment of obesity: amfepramone, benzphetamine, phendimetrazine and phentermine. The article provides an overview of both the history, and the current status, of the use of amphetamine derivatives in the obesity pharmacotherapy.


1. Hochberg Z. An evolutionary perspective on the obesity epidemic. Trends Endocrinol Metab 2018;29(12):819-26.
2. Ghanemi A, St-Armand J. Redefining obesity toward classifying as a disease. Eur J Intern Med 2018;55:20-2.
3. Golden A. Current pharmacotherapies for obesity: a practical perspective. J Am Assoc Nurse Pract 2017;29(S1):S43-S52.
4. Haslam D. Weight management in obesity-past and present. Int J Clin Pract 2016;70(3):206-17.
5. Coulter AA, Rebello CJ, Greenway FL. Centrally acting agents for obesity: past, present, and future. Drugs 2018;78(11):1113-32
6. Ioannides-Demos LL, Proietto J, McNeil JJ. Pharmacotherapy for obesity. Drugs 2005;65(10):1391-418.
7. Kang JG, Park CY. Anti-obesity drugs: a review about their effects and safety. Diabetes Metab J 2012;36(1):13-25
8. Müller TD, Clemmensen C, Finan B, DiMarchi RD, Tschöp MH. Anti-Obesity Therapy: from rainbow pills to polyagonists. Pharmacol Rev 2018;70(4):712-46.
9. Ricca V, Castellini G, Mannucci E, et al. Amphetamine derivatives and obesity. Appetite 2009;52(2):405-9.
10. Mariotti C, Rossato LG, Froehlich PE, Limberger RP. Amphetamine-type medicines: a review of pharmacokinetics, pharmacodynamics, and toxicological aspects. Curr Clin Pharmacol 2013;8(4):350-7.
11. Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR. New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol 2007;47:681-98
12. Igel LI, Kumar RB, Saunders KH, Aronne LJ. Practical use of pharmacotherapy for obesity. Gastroenterology 2017;152(7):1765-79.
13. Onakpoya IJ, Heneghan CJ, Aronson JK. Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. BMC Med 2016;14:191.
14. Heal DJ, Smith SL, Gosden J, Nutt DJ. Amphetamine, past and present-a pharmacological and clinical perspective. J Psychopharmacol 2013;27(6):479-96.
15. Kramer MS, Lane DA. Aminorex, dexfenfluramine, and primary pulmonaryhypertension. J Clin Epidemiol 1998; 51(4):361-4.
16. Michelakis ED, Weir EK. Anorectic drugs and pulmonary hypertension from the bedside to the bench. Am J Med Sci 2001;321(4):292–9.
17. Pinder RM, Brogden RN, Sawyer PR, Speight TM, Avery GS. Fenfluramine: a review of its pharmacological properties and therapeutic efficacy in obesity. Drugs 1975;10(4):241-323.
18. Li Z, Hong K, Yip I, et al. Body weight loss with phentermine alone versus phentermine and fenfluramine with very-low-calorie diet in an outpatient obesity management program: a retrospective study. Curr Ther Res Clin Exp 2003;64(7):447-60.
19. Guy-Grand B, Crepaldi G, Vre P, Apfelbaum M, Gries A, Turner P. International trial of long-term dexfenfluramine in obesity. Lancet 1989;334(8672):1142-5.
20. Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine–phentermine. N Engl J Med 1997;337(24):581-8.
21. Gelvin EP, McGavack TH, Kengsberg S. Phenmetrazine in the management of obesity. Am J Dig Dis 1956;1(4):155-9
22. Oswald I, Thacore VR. Amphetamine and phenmetrazine addiction. Br Med J 1963;2(5354):427-31.
23. Haddler AJ. Sustained-action phendimetrazine in obesity. J Clin Pharmacol J New Drugs 1968;8(2):113-117
24. Greenway FL. Clinical studies with phenylpropanolamine: a metaanalysis. Am J Clin Nutr 1992;55(S1): S203– S205.
25. Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000;343(25):1826–32.
26. Stock MJ. Sibutramine: a review of the pharmacology of a novel anti-obesity agent. Int J Obes Relat Met Disord 1997;21(S1):S25-S29.
27. Fujioka K, Seaton TB, Rowe E, et al. Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus. Diabetes Obes Metab 2000;2(3):175-87.
28. Caterson ID, Finer N, Coutinho W, et al. Maintained intentional weight loss reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. Diabetes Obes Metab 2012;14(6):523-30.
29. Pittler MH, Ernst E. Dietary supplements for body-weight reduction: a systematic review. Am J Clin Nutr 2004;79(4):529-36.
30. Cercato C, Roizenblatt VA, Leanca CC, et al. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of diethylpropion in the treatment of obese subjects. Int J Obes 2009;33(8):857-65.
31. Lucchetta RC, Riveros BS, Pontarolo R, et al. Systematic review and meta-analysis of the efficacy and safety of amfepramone and mazindol as a monotherapy for the treatment of obese or overweight patients. Clinics 2017;72(5):317-24.
32. Lucchetta RC, Riveros BS, Pontarolo R, et al. Diethylpropion and mazindol: An end to the discussion? Rev Assoc Med Bras 2017;63(3):203-6.
33. Simkin B, Wallace L. A controlled clinical trial of benzphetamine (Didrex) in the management of obesity. Curr Ther Res Clin Exp 1960;2:33-8.
34. Musshoff F. Illegal or legitimate use? Precursor compounds to amphetamine and methamphetamine. Drug Metab Rev 2000;32(1):15-44.
35. Douglas A, Douglas JG, Robertson CE, Munro JF. Plasma phentermine levels, weight loss and side-effects. Int J Obes 1983;7(6):591-5.
36. Lewis KH, Fischer H, Ard J, et al. Safety and effectiveness of longer-term phentermine use: clinical outcomes from an electronic health record cohort. Obesity 2019;27(4):591-602.
37. Smith SM, Meyer M, Trinkley KE. Phentermine/topiramate for the treatment of obesity. Ann of Pharmacother 2013;47(3):340-9.
38. Munro JF, MacCuish AC, Wilson EM, Duncan LJ. Comparison of continuous and intermittent anorectic therapy in obesity. Br Med J 1968;1(5588):352–4.
39. Suplicy H, Boguszewski CL, dos Santos CM, do Desterro de Figuereido, Cunha DR, Radominiski R. A comparative study of five centrally acting drugs on the pharmacological treatment of obesity. Int J Obes 2014; 38(8):1097-1103.
40. Bragg R, Crannagge E. Review of pharmacotherapy options for the management of obesity. J Am Assoc Nurse Pract 2016;28(2):107-15.
41. Himmerich H, Treasure J. Psychopharmacological advances in eating disorders. Expert Rev Clin Pharmacol 2018;11(1):95-108.
How to Cite
Stăcescu Ștefana, Hancu G, Podar D, Todea Ștefania, Tero-Vescan A. A Historical Overview Upon the Use of Amphetamine Derivatives in the Treatment of Obesity. J Pharm Care. 7(3):72-79.
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