Fenfluramine is an amphetamine-derived substance first developed in the late 1960s for appetite control. Because of its known side effects at therapeutic doses, it is now controlled by the government and has been withdrawn from the market, but the underground market is still big. When over-dosed, it can produce a wide range of neurologic and cardiovascular symptoms, and even death, when a large amount is ingested. We report two cases of acute fenfluramine overdose: a fatal case with generalized seizure and pulseless electrical activity, and a case of relatively mild intoxication.
Appetite ; Fenfluramine* ; Seizures

AIMTo find the cause of abnormal NMR spectra of lomerizine dihydrochloride, cetirizine dihydrochloride and flenfluramine camphoramide.

METHODSHypothesizing, in given conditions, there are changes of stereoisomeric conformation and configuration in structure of N-containing compounds, it results in abnormality of NMR spectra. By using the method of NMR, it is confirmed credibily.

RESULTS AND CONCLUSIONThe moving balance exists between two chair conformations in lomerizine dihydrochloride and cetirizine dihydrochloride. It causes that spin-nuclei of whole molecule are placed in two chemical circumstance. In solution of DMSO-d6, the speed of conformation reversal equals to the NMR time scale, so that chemical shift of spin-nuclei can not be definitely determined, peaks are broadened and even collapsed. After dropping D2O or increasing the temperature, the viscosity of the solution is decreased, the speed of reversal is quicker than NMR time scale, then normal spectra are obtained. Owing to the reversal of the three bonds of nitrogen in flenfluramine camphoramide is limited, other pair of diastereoisomer resulted from the asymmetric nitrogen can be detected by NMR. Multiplication of the peaks of 13CNMR is reasonably explained.

Cetirizine ; chemistry ; Fenfluramine ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Conformation ; Piperazines ; chemistry

Recently over 500 victims with toxic hepatitis associated with some sort of Chinese diet food for weight reduction were developed in Japan, China, Singapore and Malaysia. These Chinese goods contain several kinds of Chinese herbs and fenfluramine, the well known anti-appetite drug. However, until today, it is not determined which component of the diet food is responsible for the hepatic injury. Nowadays, toxic hepatitis is frequently seen in daily practice, second only to viral origin in Korea. We present a 38-year-old woman who developed mixed cholestatic and hepatocellular injury after 5 week's ingestion of the Chinese diet food. The causality of this agent to the hepatotoxicity was assessed by RUCAM and M and V scale. Herein we described the clinical course and liver pathology of this patient.
Adult ; Asian Continental Ancestry Group* ; China ; Diet* ; Drug-Induced Liver Injury* ; Eating ; Female ; Fenfluramine ; Humans ; Japan ; Korea ; Liver ; Malaysia ; Pathology ; Singapore ; Weight Loss

There have recently been many advances in obesity treatment, including lifestyle modifications and pharmacological and surgical treatments. Specifically, pharmacological strategies have improved significantly. However, the history of the development of medications aimed at weight loss is complicated. The Federal Drug Administration (FDA) withdrew anti-obesity drugs such as fenfluramine, dexfenfluramine, and phenylpropylamine due to their unwanted side effects. Moreover, sibutramine was voluntarily withdrawn from the market and a new drug, rimonabant, has been suspended in the middle of a clinical trial due to unacceptable side effects. The FDA has approved four new anti-obesity drugs in recent years. Lorcaserin is a selective 5-hydroxytryptamine receptor 2c (5-HT2c) agonist. The pharmacological mechanism of action of this drug is similar to fenfluramine and dexfenfluramine, but lorcaserin is specific for 5-HT2c, which are located almost exclusively in the central nervous system and are not found in heart valves. Three phase 3 clinical trials for lorcaserin have been published recently; weight reduction was successful and no side effects involving the heart were found. Furthermore, the FDA has also approved phentermine/topiramate controlled-release (PHEN/TPM CR), which is composed of a combination of immediate-release phentermine and controlled-release topiramate. Weight reduction achieved with PHEN/TPM CR was demonstrated to be better than all other anti-obesity drugs. Lastly, the combination therapy bupropion/naltrexone activates proopiomelanocortin neurons and inhibits opioid-mediated negative feedback by synergism. Similar to liraglutide, a long-acting analogue of the hormone glucagon-like peptide-1, this treatment showed significant weight loss and metabolic improvements. However, in addition to its efficacy, clinicians should consider its side effects before use.
Anti-Obesity Agents ; Central Nervous System ; Dexfenfluramine ; Fenfluramine ; Glucagon-Like Peptide 1 ; Heart ; Heart Valves ; Life Style ; Neurons ; Obesity* ; Phentermine ; Pro-Opiomelanocortin ; Serotonin ; Weight Loss ; Liraglutide

Along with psychosocial factors of suicide, biological backgrounds of suicide are explored by extensive works mostly on biological markers, neurobiological models, genetic bases, and relationship with aggression and violence. The biology of suicide confers on neurotransmitters in central nervous system exploring metabolites, receptor binding affinities, neuroen-docrine challenge tests in brain, cerebrospinal fluid, blood and etc. The major concerns with suicide are focused mainly on serotomin system: low CSF-5-HIAA concentration, higher 5-HT2 receptor binding, and blunt prolactin response to fenfluramine. Postmortem study, in vivo study, genetic contributions, and some other issues such as suicidal methods, serum cholesteral, alcohol, and selective serotonin reuptake inhibitors are reviewed and discussed.
Aggression ; Biomarkers ; Biology ; Brain ; Central Nervous System ; Cerebrospinal Fluid ; Fenfluramine ; Models, Genetic ; Neurotransmitter Agents ; Pathology* ; Prolactin ; Psychology ; Serotonin Uptake Inhibitors ; Serotonin* ; Suicide* ; Violence*

The clinical efficacy of serotonin reuptake inhibitors such as clomipramine in the treatment of obsessive compulsive disorder(OCD) has fueled interest in the neurobiological basis of the illness. OCD is responsive exclucively to potent serotonin reuptake clomipramine, fluoxetine, fluvoxamine, sertraline, and paroxetine and the point forms the important evidence supporting a cental role for serotonin in the pathogenesis of the disorder. Other serotonergic medications such as lithium, buspirone, trazodone, or fenfluramine may be useful as adjuvant treatments in treatment-refractory OCD and adjuvant antipsychotics are useful in tic disorder, personality disorders, and psychotic disorders. This paper reviews results of treatment studies, investigations of biological markers, and neuroendocrine challenges and implications for the role of serotonin in pathophysiology and treatment of OCD.
Antipsychotic Agents ; Biomarkers ; Buspirone ; Clomipramine ; Fenfluramine ; Fluoxetine ; Fluvoxamine ; Lithium ; Obsessive-Compulsive Disorder ; Paroxetine ; Personality Disorders ; Psychotic Disorders ; Serotonin Uptake Inhibitors ; Serotonin* ; Sertraline ; Tic Disorders ; Trazodone

There have been many advances in obesity treatment, including life-style modification and pharmacological and surgical treatments. It seems that the most remarkable advances in obesity treatment are those of pharmacological strategies. However, weight loss medications have a long history of development. The FDA has withdrawn anti-obesity drugs such as fenfluramine, dexfenfluramine, and phenylpropylamine due to unwanted side effects. Sibutramine was voluntarily withdrawn from the market, and new drugs such as rimonabant have been suspended in the middle of clinical study due to unacceptable side effects. Last year, the FDA approved two new anti-obesity drugs for the treatment of obesity. Lorcaserin is a selective 5-hydroxytryptamine receptor 2c (5-HT2c) agonist whose pharmacological mechanism of action is similar to those of fenfluramine and dexfenfluramine. However, lorcaserin is specific for 5-HT2c, which is located almost exclusively in the CNS and is not found on heart valves. Three exciting phase 3 clinical trials for lorcaserin have been published recently. Lorcaserin has been shown to successfully result in weight reduction, and the drug was not found to lead to heart disease, as is the case with some other such drugs. Furthermore, the FDA also approved controlled release phentermine/topiramate (PHEN/TPM CR), a drug composed of immediate-release phentermine and controlled-release topiramate. Weight reduction by PHEN/TPM CR is better than any other anti-obesity drugs in the world. Along with this excellent efficacy, however, come painful side effects that clinicians should consider.
Anti-Obesity Agents ; Benzazepines ; Cyclobutanes ; Dexfenfluramine ; Fenfluramine ; Fructose ; Heart Diseases ; Heart Valves ; Obesity ; Phentermine ; Piperidines ; Pyrazoles ; Serotonin ; United States Food and Drug Administration ; Weight Loss