Valvular Heart Disease Associated with Fenfluramine–Phentermine

Connolly, Heidi M.; Crary, Jack L.; McGoon, Michael D.; Hensrud, Donald D.; Edwards, Brooks S.; Edwards, William D.; Schaff, Hartzell V.

doi:10.1056/nejm199708283370901

Cited by 1,470 publications

(725 citation statements)

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“…Most are not realistic for human use. Fenfluramine, despite being an efficient way to increase 5-HT in animals, cannot readily be administered to human subjects in high doses (Connolly et al, 1997), although one study has now published preliminary findings using an oral dose to increase brain 5-HT (Hasler et al, 2009). The SSRIs are a safe option and intravenous preparations of citalopram can be obtained for use in infusion paradigms (Marner et al, 2010;Pinborg et al, 2004).…”

Section: Nature Of the Serotonergic Challengementioning

confidence: 99%

Measuring Endogenous 5-HT Release by Emission Tomography: Promises and Pitfalls

Paterson

Tyacke

Nutt

et al. 2010

J Cereb Blood Flow Metab

128

137

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Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron emission tomography, but has not yet been adequately extended to other neurotransmitter systems. This review focuses on how the technique has been applied to the study of the 5-hydroxytryptamine (5-HT) system. The principles behind visualising fluctuations in neurotransmitters are introduced, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT 1A , 5-HT 2A , and 5-HT 4 receptors and the serotonin reuptake transporter have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made as to how the selection of targets, radiotracers, challenge paradigms, and experimental design might be optimised to improve our chances of successfully imaging endogenous neurotransmitters in the future.

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Section: Nature Of the Serotonergic Challengementioning

confidence: 99%

Measuring Endogenous 5-HT Release by Emission Tomography: Promises and Pitfalls

Paterson

Tyacke

Nutt

et al. 2010

J Cereb Blood Flow Metab

128

137

View full text Add to dashboard Cite

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“…However, after reports of adverse cardiopulmonary events, the Food and Drug Administration withdrew d-Fen from clinical use in 1997. 193 Nevertheless, the existence of 5-HTresponsive POMC cells strongly suggests that the central melanocortin system contributes to the anorectic effects of 5-HT. It is also interesting to speculate based on the observation that auto-antibodies are raised against a-MSH and adrenocorticotropic hormone in patients with anorexia and bulimia nervosa.…”

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confidence: 99%

Body weight is regulated by the brain: a link between feeding and emotion

2005

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Regulated energy homeostasis is fundamental for maintaining life. Unfortunately, this critical process is affected in a high number of mentally ill patients. Eating disorders such as anorexia nervosa are prevalent in modern societies. Impaired appetite and weight loss are common in patients with depression. In addition, the use of neuroleptics frequently produces obesity and diabetes mellitus. However, the neural mechanisms underlying the pathophysiology of these behavioral and metabolic conditions are largely unknown. In this review, we first concentrate on the established brain machinery of food intake and body weight, especially on the melanocortin and neuropeptide Y (NPY) systems as illustration. These systems play a critical role in receiving and processing critical peripheral metabolic cues such as leptin and ghrelin. It is also notable that both systems modulate emotion and motivated behavior as well. Secondly, we discuss the significance and potential promise of multidisciplinary molecular and neuroanatomic techniques that will likely increase the understanding of brain circuitries coordinating energy homeostasis and emotion. Finally, we introduce several lines of evidence suggesting a link between the melanocortin/NPY systems and several neurotransmitter systems on which many of the psychotropic agents exert their influence. Maintaining energy homeostasis is fundamental for survival. However, obesity due to over-nutrition is an increasing worldwide public health problem. 1 In psychiatric practice, on the other hand, impaired appetite is one of the crucial issues. Anorexia and weight loss are common, for example, in patients suffering from depression. Eating disorders are medically intractable and life threatening. In addition, the so-called 'atypical' antipsychotic agents, currently and widely used to treat psychoses, often induce hyperphagia, obesity, and diabetes mellitus. [2][3][4] In the past decade, fortunately, there has been remarkable progress in understanding the molecular mechanisms of food intake and body weight. This is due in large part to increased research activity towards combating the rising incidences of obesity and associated metabolic disorders. As a result, it is now established that the central nervous system (CNS) senses and processes peripheral metabolic cues including leptin 5 and ghrelin, 6,7 resulting in coordinated energy homeostasis. However, the pathophysiology of the disequilibrium between energy intake and expenditure in psychiatric disorders remains largely unknown. Nevertheless, evidence suggests that several CNS systems regulating energy balance may be dysregulated in patients with mental illnesses, for example, eating disorders, and drug addiction. [8][9][10][11][12][13][14] In the current review, we will illustrate the neuroanatomic and molecular genetic aspects of the melanocortin and neuropeptide Y (NPY) systems residing in the CNS downstream of leptin and ghrelin, to discuss the neural bases of feeding, metabolism, and emotion. Additionally, we point the reader to...

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“…The amphetamine derivatives d,l-fenfluramine (FEN) and d -fenfluramine (dFEN) were widely prescribed appetite suppressants until their removal from the market due to serious side-effects (Connolly et al 1997). In laboratory animals, high-dose administration of FEN or dFEN causes long-term ( Ͼ 2 weeks) degeneration of serotonin (5-HT) nerve terminals throughout the forebrain (reviewed by McCann et al 1997).…”

mentioning

confidence: 99%