Americans' desire to lose weight has been a driving force behind the use of appetite-suppressing medications for over half a century. In 1959, phentermine became the first prescription appetite suppressant approved by the U.S. Food and Drug Administration. Fenfluramine received FDA approval in 1973, and in 1996 dexfenfluramine, or Redux, got the nod for the treatment of obesity. Fenfluramine, dexfenfluramine and phentermine enjoyed widespread use until 1997, when the first reports of drug-related heart damage began to surface.
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Serotonin is intimately involved with appetite control. Food consumption triggers reflexes that increase serotonin levels in specific centers of your brain, thereby signaling a sense of fullness. A study published in the July 2006 issue of the journal "Neuron" demonstrated that fenfluramine and dexfenfluramine stimulated serotonin receptors in the appetite centers of the central nervous system, thereby mimicking a constant state of having eaten. This, in turn, led to decreased caloric intake and eventual weight loss.
Heart Damage
The first cases of heart damage caused by fenfluramine-like drugs involved injury to the valves that control the flow of blood through the heart. Heart valves are among the many tissues outside the central nervous system that have serotonin receptors. The excessive stimulation of these receptors by serotonin look-alikes fenfluramine and dexfenfluramine contributed to valvular injury and, subsequently, to valve failure for nearly one-quarter of surveyed patients.
Pulmonary Arterial Hypertension
The pulmonary artery is the vessel that carries deoxygenated blood from the right side of the heart toward the lungs, where it receives a fresh supply of oxygen before returning to the left side of the heart. If the blood vessels in the lungs become constricted for any reason, the pressure within the entire pulmonary system increases, placing a strain on the right side of the heart. The June 2008 issue of "Circulation" described a study that demonstrated the presence of serotonin receptors within the vessels of mammalian lung. When stimulated by dexfenfluramine and similar agents, these receptors trigger vascular constriction, which raises pulmonary pressures in the short term. Over longer periods of time, the blood vessels undergo structural changes that make the condition difficult to reverse.
Considerations
In September 1997, fenfluramine and dexfenfluramine were withdrawn from the American market. By that time, ongoing studies of people taking these medications revealed that 30 percent of them had an abnormal echocardiogram, which is a study used to evaluate your heart valves. The drugs' role in the genesis of pulmonary hypertension has since been clearly established. Lessons learned from studying pulmonary hypertension in individuals who took appetite suppressants may prove useful in treating pulmonary hypertension caused by other conditions.
References
- "Morbidity and Mortality Weekly Report"; Cardiac Valvulopathy Associated with Exposure to Fenfluramine or Dexfenfluramine: U.S. Department of Health and Human Services Interim Public Health Recommendations, November 1997
- "Neuron"; Serotonin Reciprocally Regulates Melanocortin Neurons to Modulate Food Intake; L.K. Heisler, et al.; July 2006
- "Circulation"; Converging Evidence in Support of the Serotonin Hypothesis of Dexfenfluramine-Induced Pulmonary Hypertension with Novel Transgenic Mice; Y. Dempsie, et al.; June 2008
- U.S. Food and Drug Administration: FDA Announces Withdrawal Fenfluramine and Dexfenfluramine (Fen-Phen)
