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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obese subjects show a subnormal growth hormone (GH) and prolactin (PRL) release in response to a variety of stimuli. Fenfluramine, an anorexiant drug used in obesity therapy, may have some effects on hypothalamic-pituitary function mediated by serotoninergic stimulation. The present investigation in obese subjects was carried out to study the effects of fenfluramine (60 mg orally) on GH and PRL secretion after intravenous arginine infusion. Ten volunteer obese females were studied and compared with 10 volunteer normal weight controls. In the obese group the GH response to arginine was significantly lower than in control group. Fenfluramine administration restored the subnormal GH response to arginine in obese subjects. The PRL response to arginine in obese women was subnormal. Fenfluramine administration restored the response of PRL to arginine infusion to normal. In conclusion, fenfluramine--under acute circumstances--enhances the hypothalamic-pituitary response to arginine in obese subjects. The decreased GH and PRL output in obese subjects is not due to an absolute hormonal deficiency and this effect of fenfluramine on GH secretion may--due to its lipolysis stimulation--be useful in obesity treatment.
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PMID:Effect of fenfluramine on growth hormone and prolactin secretion in obese subjects. 343 16

Fenfluramine, an anorectic used in the treatment of obesity, in a final concentration of 1 mM strongly inhibited both phases of insulin release by the perfused rat pancreas. Insulin secretion resumed promptly after cessation of the drug infusion. This concentration of the drug markedly increased glucagon output. The blockade of alpha-adrenergic receptors and the use of antiserotonin agents did not alter the inhibitory effect of fenfluramine on insulin secretion. It is concluded that in the perfused rat pancreas 1 mM fenfluramine acutely inhibits glucose-induced insulin secretion and potentiates glucagon output. The direct effect of fenfluramine on insulin secretion is not related to alpha-adrenergic activity, nor is it mediated by serotonin.
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PMID:Fenfluramine inhibits insulin secretion and potentiates glucagon release by the perfused rat pancreas. 622 12

The currently available antiobesity drugs will produce an additional mean weight loss of approximately 0.5 lb (0.23kg) per week for a limited period of time. There is no major difference between the weight losing properties of the various drugs, and choice of drug depends in part on other factors such as cost and side effects. Those drugs affecting catecholaminergic pathways such as phentermine and diethylpropion can be prescribed intermittently because this is as effective, cheaper and presumably less likely to result in dependence than continuing therapy. Fenfluramine however is best given continuously, the dose being built up and reduced stepwise to avoid the dangers of withdrawal depression. Individual response may depend partly upon drug compliance and metabolism but cannot be predicted except by trial and error. Once a drug is discontinued, weight regain is the rule and there is no evidence that drug therapy helps to re-educate faulty eating habits. It follows that therapy can be most easily justified if there is a short term need to achieve weight loss, e.g. prior to elective surgery. In some patients, weight regain may be prevented by giving the drug long term but the complications of long-term administration have yet to be evaluated. If it can be justified at all, it is in those subjects with complicated obesity. The development of a non-pharmacological way of preventing weight regain following drug therapy would enhance the potential usefulness of an antiobesity agent.
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PMID:The current status of antiobesity drugs. 639 7

The effects of behavior therapy with and without either pharmacotherapy or couples training were studied in 124 obese adults. In a 16-week behavioral weight-reduction program, patients were assigned to medication (fenfluramine hydrochloride) and no-medication conditions and to three spouse conditions in a 2 x 3 design. Two conditions consisted of patients with "cooperative" spouses; in one, patients were treated with their spouses, and in the other they were treated alone. In the third, patients with "uncooperative" spouses were treated alone. Fenfluramine produced significantly greater weight losses than no medication, but patients in the medication group regained weight much more rapidly during a 12-month maintenance period. The spouse conditions did not differ in weight change during treatment or follow-up. Obese spouses lost as much weight as the patients and were slightly more successful than the patients at maintaining their losses. Patients with obese spouses lost more weight than patients with nonobese spouses. Depression decreased in proportion to decrease in weight.
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PMID:Couples training, pharmacotherapy, and behavior therapy in the treatment of obesity. 730 2

A comparison has been made of the effects of d(+) fenfluramine, Mazindol and Diethylpropion on the changes in body weight and brain ascorbic acid concentrations in male and female guinea pigs receiving vitamin C-deficient diet daily with or without daily supplementary vitamin C for 24 days. Bodyweight increases initially; the subsequent decrease was more rapid in scorbutic male than in the female guinea pigs. The weight-reducing drugs prevented the initial rise in weight of these ascorbutic guinea pigs. Fenfluramine caused the greatest fall in weight in both sexes, the effect being more pronounced in the males. Supplementary vitamin C reduced the anti-obesity actions of fenfluramine, Mazindol and Diethylpropion. Brain ascorbic acid level in scorbutic guinea pigs was more significantly reduced by fenfluramine than by either Mazindol or Diethylpropion after 24 days administration. These drugs prevented the rise in brain ascorbic acid normally produced by supplementary vitamin C. The reduction brain ascorbic acid appears to be related to the loss of weight more in the males than in the females.
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PMID:Vitamin C and weight reducing drugs on brain ascorbic acid in guinea pigs. 732 3

Fenfluramine (Fen), an amphetamine-derivative widely used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice for assessing its clastogenic potentials. Concentrations of 0.75, 1.50 and 5.0 mg Fen/kg body weight (b.w.) were administered orally for the study. Long-term treatment for 21 days showed dose-dependent significant increase in chromosomal aberrations on the 8th day. A significant decrease in aberration levels was seen in the late treatment period. Caffeine alone produced dose- and duration-dependent clastogenicity at doses of 2.0, 4.0 and 6.0 mg/kg b.w. when given by gavage. Using caffeine post-treatment (4.0 and 6.0 mg/kg b.w.) 2 h after Fen application, a strong synergism could be seen in the late treatment period as shown by the dose-response curves and by statistical analysis using the principle of least squares. The results support the hypothesis that prolonged Fen application induces dose-dependent increase in post-replication repair and caffeine enhanced toxicity by inhibiting repair process(es). The study suggests that Fen is a clastogen and since caffeine may have a synergistic effect, it should be avoided during treatment.
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PMID:Potentiation by caffeine of the frequencies of chromosomal aberrations induced by chronic exposure to fenfluramine in mice. 806 39

d-Fenfluramine is an appetite suppressant drug that acts by releasing serotonin from axon terminals and inhibiting its reuptake. S 5B/P1 rats, which are resistant to dietary-fat induced obesity, and Osborne-Mendel rats, which are sensitive, were adapted to ad lib feeding of either a low- or high-fat diet. d-Fenfluramine (10 mg/kg, IP) was injected daily for 12 days. Other than a slightly greater suppression of food intake in Osborne-Mendel rats, there was little difference in response to d-fenfluramine between S 5B/P1 and Osborne-Mendel rats eating the low-fat diet. However, in Osborne-Mendel rats d-fenfluramine completely abolished the excess food intake and weight gain associated with the high-fat diet. Purine nucleotide (GDP) binding on day 13 was higher in S 5B/P1 rats than in Osborne-Mendel rats and was increased by d-fenfluramine in animals of both strains eating the low-fat diet. The high-fat diet increased GDP binding only in S 5B/P1 rats and blocked the fenfluramine-induced increase in GDP binding in both strains. We speculate that d-fenfluramine blocks a feeding reward system stimulated by the high-fat diet.
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PMID:d-fenfluramine in a rat model of dietary fat-induced obesity. 832 56

d Fenfluramine (dF) (15 mg twice daily) has been studied in controlled trials in human obesity. It has been shown to increase adherence to weight lowering programs, to double the number of patients losing 10 kg or more when compared with a fairly efficient placebo plus dietary counselling, and to prevent weight regain when continued over a 1 year period. Weight loss after 1 month and 4 months is likely to predict subsequent outcome. Also, significant improvement in metabolic risk factors and blood pressure were clearly demonstrated, even more markedly in some obesity-associated diseases, when body weight is maintained at a lower level. Even moderate but sustained weight loss of some 10% of starting weight or less has been confirmed to be of medical value. Tolerance and safety of dF can be considered acceptable, even if longer term follow-up is clearly needed. These studies support the concept that long-term pharmacotherapy with this serotoninergic drug might help achieve better outcome in the management of many obese patients, particularly in preventing relapse. The long-term managerial strategies to be developed for each patient might thus include dF together with dietary advice, behavioral modification and physical exercise, either simultaneously or sequentially.
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PMID:Clinical studies with dexfenfluramine: from past to future. 869 48

The combined administration of phentermine and fenfluramine (PHEN/FEN) has been used as a treatment for obesity. Recent evidence suggests that this drug mixture may also be an effective medication for substance abuse disorders, including cocaine dependence. It is well-established that repeated high-dose fenfluramine causes serotonin (5-HT) terminal degeneration in laboratory animals, and no studies have addressed possible interactions between phentermine and fenfluramine. The purpose of the present work was to examine the effect of phentermine coadministration on fenfluramine-induced depletion of 5-HT in mouse forebrain. In addition, because of the potential for cocaine abuse in drug addicts taking PHEN/FEN as a medication, we examined the effects of PHEN/FEN on forebrain 5-HT levels in the presence or absence of cocaine. Fenfluramine (0, 3, 10, 30 mg/kg, s.c. twice daily for 4 days) caused a dose-dependent reduction in forebrain 5-HT without affecting dopamine or norepinephrine. Phentermine coadministration (7 mg/kg, s.c. twice daily for 4 days) did not significantly alter the 5-HT-depleting effect of fenfluramine. Likewise, cocaine (10 mg/kg, i.p.), administered 60 min prior to or 60 min after PHEN/FEN, had no effect on the PHEN/FEN-induced decrease in central 5-HT. The present results indicate that doses of phentermine far above those typically administered to humans do not potentiate the 5-HT-depleting effect of repeated high-dose fenfluramine. Moreover, exposure to cocaine does not significantly alter the long-term neurochemical actions of the PHEN/FEN mixture.
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PMID:Effects of phentermine and cocaine on fenfluramine-induced depletion of serotonin in mouse brain. 879 12

The medical risks of obesity increase exponentially as weight increases, and these risks are reduced by sustained weight loss. Behavior modification and dieting provide an approximately 6% loss of body weight at 1 year. Fenfluramine provides an approximately 8% weight loss at 1 year, which can be doubled to 16% when a drug such as phentermine, which works through a different biochemical mechanism, is added to it. This amount of weight loss is insufficient for many severely obese individuals. It was with these facts in mind that the National Institutes of Health Consensus Conference in 1992 recommended that obesity surgery is an appropriate treatment for patients with a body mass index greater than 40 kg/m2 who had failed in attempts at medical treatment and for patients with a body mass index greater than 35 kg/m2 with severe complications of obesity. Vertically banded gastroplasty and Roux-en-Y gastric bypass are the two operations presently recommended because of their relative safety and effectiveness. This article reviews previous procedures that have provided insight into the mechanisms by which these surgeries cause weight loss. The presently used surgeries and their results also are reviewed because until medical therapy improves substantially, surgery remains the most reasonable treatment option for most morbidly obese patients.
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PMID:Surgery for obesity. 897 58


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