Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dexfenfluramine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dexfenfluramine-associated changes in 5-hydroxytryptamine transporter expression and development of hypoxic pulmonary hypertension in rats.

The appetite suppressant dexfenfluramine, which inhibits neuronal 5-HT uptake and elevates plasma 5-HT levels, has been associated with an increase in the relative risk of developing primary pulmonary hypertension. 5-HT is a mitogen for pulmonary artery smooth muscle cells (PA-SMCs), an effect that depends upon activity of the 5-HT transporter (5-HTT). To investigate the relationship between dexfenfluramine and pulmonary hypertension, we examined 1) the effect of dexfenfluramine on 5-HT uptake by PA-SMCs and the mitogenic response of these cells to 5-HT, and 2) 5-HTT mRNA in lung tissue from normoxic and chronically hypoxic rats during and at discontinuation of a 4-week dexfenfluramine treatment (2 mg/kg/day). In cultured PA-SMCs, dexfenfluramine (10(-6) M) markedly reduced [3H]5-HT uptake and [3H]thymidine incorporation in response to 5-HT (10(-6) M). In lungs from rats exposed to 4-week hypoxia (10% O(2)), 5-HTT mRNA levels were higher than in normoxic rats (233.5 +/- 22.5 versus 121.8 +/- 4.8 amol/mg of RNA, P < 0.05), but were not affected by concomitant treatment with dexfenfluramine. One week after discontinuation of dexfenfluramine, 5-HTT mRNA levels increased substantially, this effect being additive with that of hypoxia (364.0 +/- 13.1 in hypoxic versus 164.2 +/- 10 amol/mg of RNA in normoxic rats). When exposure to 2 weeks of hypoxia followed discontinuation of a 4-week treatment, right ventricular hypertrophy was more severe and muscularization of distal pulmonary arteries more marked (P < 0.01) than in rats pretreated with the vehicle. These data show that, in rats, the increased 5-HTT expression that follows dexfenfluramine discontinuation promotes the development of hypoxic pulmonary hypertension.

Animals↗
PubMed1996

Evaluation of dexfenfluramine in a weight loss program for obese infertile women.

OBJECTIVE: To evaluate the usefulness of dexfenfluramine as an adjunct to a group treatment program for obese infertile women. METHOD: Twenty-one obese infertile women were referred by the Reproductive Medicine Unit. They attended a 24-week group program which included exercise and educational sessions. Dexfenfluramine and placebo were given, each for 12 weeks, in a double-blind crossover design. RESULTS: Dexfenfluramine treatment was not associated with greater loss of weight. The mean weight loss during dexfenfluramine treatment was 3.21 kg (SD 3.09) and during placebo was 3.31 kg (SD 3.15). Self-esteem, anxiety, and depression ratings all improved significantly over the 24 weeks. DISCUSSION: The group treatment program appeared to be equally effective with or without dexfenfluramine. Previous studies have found dexfenfluramine to be effective in combination with individual treatment, but it has not previously been evaluated as an adjunct to group treatment. It is unclear whether dexfenfluramine may be less effective in combination with group treatment programs, or whether its usefulness is restricted in this particular population of obese patients. No differences were found associated with the order in which active and placebo treatments were given. Patients showed improvement in self-esteem and reduction in depression and anxiety, but dexfenfluramine treatment was not associated with any difference in these measures, compared to placebo.

Adult↗
PubMed1994

Dexfenfluramine-induced prolactin release as an index of central synaptosomal 5-hydroxytryptamine during treatment with fluoxetine.

Serotonin (5-HT) stimulates prolactin release. In the present study the ability of dexfenfluramine to increase serum prolactin was used as an index of central 5-HT function after acute and chronic pretreatment of volunteers with fluoxetine. Following a single-blind, random design, on each experimental day each volunteer received 60 mg dexfenfluramine taken with 250 ml water at zero time and no other treatment, or pretreatment with 40 mg fluoxetine at -8 h, or pretreatment with 20 mg fluoxetine daily for 14 days, or the dexfenfluramine alone 14 days after cessation of 14 days of fluoxetine treatment. There were no significant differences between the prolactin levels found after dexfenfluramine only, dexfenfluramine after a single dose of fluoxetine, and dexfenfluramine 14 days after cessation of fluoxetine treatment. However, baseline levels and those 3 and 4 h after dexfenfluramine administration were significantly lower after pretreatment for 14 days with fluoxetine compared to the other three regimens. At 5 h the levels were still lower, but not significantly so, as the prolactin level rose approximately 110% compared to the baseline and 4 h values. The reduction in the median basal serum prolactin level by almost two-thirds after 14 days of fluoxetine treatment suggests a decrease in 5-HT turnover. Furthermore, the delayed surge in prolactin release produced by dexfenfluramine with this regimen suggests 5-HT release from a less accessible pool or accumulation of fluoxetine in the neuronal cytosol and consequent competitive inhibition of 5-HT transport out of the nerve terminal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effect of dexfenfluramine on sleep in healthy subjects.

The acute effects of dexfenfluramine on nocturnal sleep were studied in ten healthy male subjects by means of sleep EEG recordings and ratings of subjective sleep quality. Four different dosages (3 mg, 7 mg, 15 mg, and 30 mg) were tested, administered over a period of 3 days each. Under 15 mg and 30 mg dexfenfluramine, only slight effects on sleep were observed: 15 mg led to decreased sleep efficiency in the first night of medication, and to reduced percentage of slow wave sleep in the first and third night. A significant lengthening of REM latency was present in the third night under 30 mg dexfenfluramine, without changes in other REM sleep parameters. Daily doses of 3 mg and 7 mg dexfenfluramine did not influence sleep, except for a significant REM latency reduction observed in the first night under 3 mg. Apart from a transient slight impairment under 30 mg, ratings of subjective sleep quality did not mirror any impact of dexfenfluramine. The data suggest that therapeutic dosages of dexfenfluramine only slightly influence nocturnal sleep, which contrasts with the known impact of other anti-obesity agents like the amphetamines. Unlike classical antidepressants, dexfenfluramine does not reduce REM sleep; in light of a hypothetical link between REM sleep reduction and antidepressant action of a drug, dexfenfluramine is not expected to have a pronounced antidepressant effect.

Adolescent↗
PubMed1995

Serotonin and dietary fat intake: effects of dexfenfluramine.

Traditionally, serotonin (5-HT) has been most commonly linked with carbohydrate (CHO) intake. However, in recent years it has been demonstrated that serotoninergic drugs such as dexfenfluramine also reduce energy intake and reverse body weight gain in rats exposed to weight-increasing high-fat diets. Dexfenfluramine is also effective in decreasing food intake and body weight gain of rats that gain weight on a high-fat cafeteria diet. The basic science studies indicate that serotoninergic activity--induced by dexfenfluramine--can act as a sufficient stimulus for the reduction of fat consumption. High-fat diets do not appear to impede the suppressive effect of dexfenfluramine on food intake. In human studies with dexfenfluramine, it has often been the case that the fat content of test foods has been held constant--with only protein and CHO allowed to vary. These studies therefore cannot display any direct effect on fat. However, when food choice is not limited by experimental constraints, a significant reduction of fat intake by dexfenfluramine has been demonstrated in obese patients. In other experimental studies, dexfenfluramine has suppressed fat intake to a greater extent than other macronutrients when free selection of foods has been permitted. Taken together, these studies demonstrate that dexfenfluramine is effective at reducing energy intake with a diet high in fat and may under certain conditions cause a selective avoidance of high-fat foods.

Animals↗
PubMed1994

Effect of dexfenfluramine on saccharin drinking: behavioural and pharmacological studies.

We have previously reported that the 5-hydroxytryptamine (5-HT) releaser/reuptake blocker dexfenfluramine suppresses voluntary ethanol intake. To further analyse the generality of these findings, in the present study we examined the effect of equivalent doses of dexfenfluramine (0.5-2.5 mg/kg) on the intake of another preferred fluid, saccharin. Saccharin was made available for 2 h daily across a wide concentration range chosen to promote varying degrees of intake. Following stable levels of intake, the behaviour of vehicle-pretreated rats was assessed immediately prior to (anticipatory/preparatory phase) and during (consumatory phase) saccharin access. These behaviours were compared and contrasted with those produced following dexfenfluramine pretreatment at the optimally preferred saccharin concentration (0.2%). In a preliminary study the effects of various 5-HT antagonists were also examined against the dexfenfluramine response. The present results suggest that dexfenfluramine produced a dose-related suppression of saccharin intake at doses similar to those which reduced ethanol intake. However, the magnitude of this suppression was similar across each saccharin concentration. Behavioural analysis indicated that the profile of the dexfenfluramine (0.5- and 1-mg/kg doses only) suppression of the 0.2% solution was similar to that observed in vehicle-pretreated rats presented with saccharin solutions of lesser palatability to this concentration. Pharmacological studies indicated a 5-HT1 (non-5-HT1C) receptor involvement in the dexfenfluramine response. These studies imply that at certain doses dexfenfluramine may produce a subtle alteration in the motivation to consume a preferred fluid.

Animals↗
PubMed1996

Effect of dexfenfluramine on the transcriptional activation of CRF and its type 1 receptor within the paraventricular nucleus of the rat hypothalamus.

1. The present study investigated the effect of intraperitoneal (i.p.) administration of the indirect 5-hydroxytryptamine (5-HT) receptor agonist, dexfenfluramine, on the transcriptional activity of corticotropin-releasing factor (CRF) and its type 1 receptor in the brains of conscious male Sprague-Dawley rats via in situ hybridization histochemistry (ISHH) using both intronic and exonic probe technology. 2. The immediate early gene (IEG) c-fos mRNA was also used as index of cellular activity, whereas localization between CRF-immunoreactive (ir) perikarya and the IEG was accomplished to determine the site of CRF neuronal activation in the brain of dexfenfluramine-treated rats. 3. Thirty minutes, 1, 3, and 6 h after a single injection of either dexfenfluramine (10 mg kg-1) or the vehicle solution, adult male rats (230-260 g) were deeply anaesthetized and rapidly perfused with a 4% paraformaldehyde-borax solution (PF). The brains were removed from the skull, postfixed, and placed in a solution of 4% PF-10% sucrose overnight at 4 degrees C. Frozen brains were mounted on a microtome and cut from the olfactory bulb to the medulla in 30-microns coronal sections. 4. Dexfenfluramine induced a general neuronal activation as indicated by the strong signal of c-fos mRNA in several structures of the brain, including the parietal cortex, caudate putamen, circumventricular organs, medial preoptic area, bed nucleus of the stria terminalis, choroid plexus, choroidal fissure, supraoptic nucleus, paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the thalamus, central nucleus of the amygdala, dorsomedial nucleus of the hypothalamus, laterodorsal tegmental nucleus, locus coeruleus, and several subdivisions of the dorsal vagal complex. In most of these structures, the signal was maximal at 30 min, still strong and positive at 60 min, largely decreased at 3 h, and had completely disappeared 6 h after injection. 5. In the parvocellular division of the PVN, the large majority of CRF-ir perikarya displayed a positive signal for the mRNA encoding c-fos, indicating a profound CRFergic activation within this neuroendocrine nucleus after dexfenfluramine administration. 6. Colocalization between CRF-ir neurones and c-fos positive cells was not detected in any other regions. This selective activation of PVN CRF neurones was also confirmed by the presence of CRF primary transcript; 30 min after i.p. injection of the indirect 5-HT agonist, a positive signal for CRF hnRNA was observed, specifically in the parvocellular PVN. 7. Transcription of the gene encoding the type 1 receptor for CRF was highly stimulated in the PVN following 5-HT activation. Although this hypothalamic nucleus exhibited a barely detectable signal under basal conditions, dexfenfluramine induced a strong signal of CRF1 receptor mRNA in the parvocellular PVN. Interestingly, CRF-ir neurones displayed a positive signal for the mRNA encoding the CRF1 receptor, 3 and 6 h after systemic treatment with dexfenfluramine. 8. These results indicate that although dexfenfluramine can generate a wide neuronal activation throughout the brain, this 5-HT agonist triggers the activity of CRF neurones selectively in the parvocellular division of the PVN, a mechanism possibly related to the activity of hypothalamic-pituitary-adrenal axis. Induction of CRF1 receptor mRNA in CRF cells of the PVN indicates that neuroendocrine CRF neurones can be targeted by CNS CRF under 5-HT stimulation.

Animals↗
PubMed1995

Effects of dexfenfluramine on hypoxic pulmonary vasoconstriction and embolic pulmonary hypertension in dogs.

There has been suggestion of a possible relationship between the intake of the appetite suppressant dexfenfluramine and the development of primary pulmonary hypertension. We investigated the pulmonary vascular effects of acute intravenous dexfenfluramine in pentobarbital-anesthetized dogs ventilated in hyperoxia (fraction of inspired oxygen, FIO2, 0.4) and either challenged with a FIO2 of 0.1 to induce hypoxic pulmonary hypertension (n = 20) or given autologous blood clots to induce embolic pulmonary hypertension (n = 6). Pulmonary vascular tone was evaluated by multipoint (mean pulmonary artery pressure [Ppa] - pulmonary artery occluded pressure [Ppao])/cardiac output (Q) plots. Hypoxia increased Ppa - Ppao over the entire range of Q studied, from 1.5 to 4.0 L/min/m2, in 12 dogs (responders) and had no significant effect on (Ppa - Ppao)/Q plots in 8 other dogs (nonresponders). Dexfenfluramine did not affect (Ppa - Ppao)/Q plots in 6 responders but shifted (Ppa - Ppao)/Q plots to higher pressures in hypoxia in 6 nonresponders (p < 0.001). Dexfenfluramine had no effect on (Ppa - Ppao)/Q plots in the 6 dogs with embolic pulmonary hypertension. Because dexfenfluramine has serotoninergic properties, we compared the effects of ketanserin, a serotonin (5-hydroxytryptamine, 5-HT) S2 receptor antagonist, on naturally present versus dexfenfluramine-restored hypoxic pulmonary vasoconstriction. Ketanserin did not affect hyperoxic or hypoxic pulmonary vascular tone, neither in 6 responders nor in 2 nonresponders with dexfenfluramine-restored hypoxic vasoconstriction. We conclude that dexfenfluramine restores hypoxic pulmonary vasoconstriction in dogs with weak or absent hypoxic pressor response and that this effect is unlikely to be mediated by activation of 5-HT S2 receptors.

Animals↗
PubMed1998

Effect of dexfenfluramine treatment in rats exposed to acute and chronic hypoxia.

The anorexiant dexfenfluramine, which inhibits 5-hydroxytryptamine (5-HT) uptake, has been associated with an increase in the relative risk of developing primary pulmonary hypertension. The aim of this study was to investigate in rats whether dexfenfluramine (1) alters the pulmonary vasomotor effects of 5-HT and (2) aggravates the development of pulmonary hypertension during exposure to various levels of chronic hypoxia. In isolated lungs from normoxic rats, dexfenfluramine up to 10(-4) M did not elicit any vasoactive effects, and neither did pretreatment with dexfenfluramine (10[-5] M in the perfusate) modify the vasoactive effects of 5-HT. In normoxic conscious rats, dexfenfluramine given intravenously potentiated the pulmonary pressor response to acute hypoxia (10% O2). In rats chronically treated with dexfenfluramine during a 2-wk exposure to 15% or 10% O2, plasma 5-HT concentrations were significantly increased compared with hypoxic controls, whereas no differences were found for pulmonary artery pressure, right ventricular hypertrophy, or pulmonary vessel muscularization. In contrast, a continuous 5-HT infusion providing a sustained increase in plasma 5-HT levels was associated with increased muscularization of distal pulmonary arteries in response to 10% O2. Simultaneous administration of dexfenfluramine prevented the effect of exogenous 5-HT on vascular remodeling. Our findings show that dexfenfluramine does not potentiate the development of pulmonary hypertension in rats exposed to chronic hypoxia, despite its effect on plasma 5-HT concentrations.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

A comparison of sibutramine and dexfenfluramine in the treatment of obesity.

OBJECTIVE: Because long-term weight reduction is often unsuccessful with dietary restriction alone, pharmacological agents have been used to promote weight loss. We have compared the novel (multiple monoamine neurotransmitter reuptake inhibitor) antiobesity drug sibutramine (10 mg once daily) with the extensively studied serotonin-releasing antiobesity agent dexfenfluramine (15 mg twice daily). RESEARCH METHODS AND PROCEDURES: 226 healthy outpatients (aged 18 to 65 years; body mass index > or =27 kg/m2) were included in a 12-week, randomized, double-blind, parallel group study. The main outcome measures were changes in weight, body mass index, waist and hip circumference and ratio, and safety profiles. RESULTS: Mean (+/-SEM) absolute weight loss was 4.5 +/- 0.4 kg in the sibutramine group (n = 112) and 3.2 +/- 0.3 kg in the dexfenfluramine group (n = 112) (endpoint analysis); 4.7 +/- 0.4 kg in the sibutramine group (n = 101); and 3.6 +/- 0.3 kg in the dexfenfluramine group (n = 94) (completers analysis). Comparing the two treatments under the conventional null hypothesis of equality as a secondary analysis, weight loss at endpoint in patients receiving sibutramine was significantly greater than that achieved with dexfenfluramine (p<0.05). Both drugs had similar adverse events profiles: 174 patients (77%) experienced adverse events; 17 patients withdrew due to adverse events (sibutramine, n = 6; dexfenfluramine, n = 11). Pulse rate increased significantly in sibutramine-treated patients (3.6 bpm), but decreased in dexfenfluramine-treated patients (-0.9 bpm). DISCUSSION: Sibutramine (10 mg once daily) is at least as effective as dexfenfluramine (15 mg twice daily) in achieving weight loss in patients with obesity.

Adult↗
PubMed1999

Dexfenfluramine increases pulmonary artery smooth muscle intracellular Ca2+, independent of membrane potential.

The anorexic agent dexfenfluramine causes the development of primary pulmonary hypertension in susceptible patients by an unknown mechanism that may include changes in K+-channel activity and intracellular Ca2+ concentration ([Ca2+]i). We investigated the dose-dependent effects of dexfenfluramine on [Ca2+]i, K+ current, and membrane potential in freshly dispersed rat pulmonary artery smooth muscle cells. Dexfenfluramine caused a dose-dependent (1-1,000 microM) increase in [Ca2+]i, even at concentrations lower than those necessary to inhibit K+ currents (10 microM) and cause membrane depolarization (100 microM). The [Ca2+]i response to 1 and 10 microM dexfenfluramine was completely abolished by pretreatment of the cells with 0.1 microM thapsigargin, whereas the response to 100 microM dexfenfluramine was reduced. CoCl2 (1 mM), removal of extracellular Ca2+, and pretreatment with caffeine (1 mM) reduced but did not abolish the response to 100 microM dexfenfluramine. We conclude that dexfenfluramine increases [Ca2+]i in rat pulmonary artery smooth muscle cells by both release of Ca2+ from the sarcoplasmic reticulum and influx of extracellular Ca2+.

Animals↗
PubMed1999

Prevalence and determinants of valvulopathy in patients treated with dexfenfluramine.

BACKGROUND: Valve regurgitation has been associated with dexfenfluramine, but its prevalence and severity are uncertain. Additional factors that may contribute to valve regurgitation in patients exposed to this drug are poorly understood. METHODS AND RESULTS: Echocardiography was performed on subjects recruited from 26 prescribing sites in 15 states. The total sample of 412 subjects included 172 dexfenfluramine patients and 172 unexposed controls matched for age, sex, and body mass index and 68 unmatched subjects meeting the same entry criteria (51 dexfenfluramine patients and 17 controls). Mean treatment duration was 6.9 months; mean interval from treatment discontinuation to echocardiogram was 8.5 months. Each echocardiogram was interpreted independently by 3 echocardiographers. FDA-grade regurgitation (at least mild aortic regurgitation or at least moderate mitral regurgitation) was significantly more frequent in dexfenfluramine patients (7.6% versus 2.1% for controls; P=0.01; odds ratio, 3.82). This difference was primarily due to more frequent mild aortic regurgitation in dexfenfluramine patients (6.3% versus 1.6% in controls; P<0.02; odds ratio, 4.15). No differences were found in sclerosis or mobility for either the aortic or mitral valve. Factors independently related to FDA-grade regurgitation or any grade of aortic regurgitation were older age, higher diastolic blood pressure at the time of echocardiography, and shorter time from drug discontinuation to echocardiogram. CONCLUSIONS: Dexfenfluramine use is associated with an increase in the prevalence of abnormal valve regurgitation. Age and blood pressure may also affect the prevalence of regurgitation. Dexfenfluramine-related valve regurgitation may regress after drug discontinuation.

Adult↗
PubMed2003

Dexfenfluramine and heart-valve regurgitation in Chinese patients with type 2 diabetes.

OBJECTIVE: To assess whether valvular lesions are associated with the use of dexfenfluramine in Chinese patients with type 2 diabetes. DESIGN: Case-control study. PATIENTS AND METHODS: Thirty-six obese Chinese patients with type 2 diabetes and a history of dexfenfluramine use during the period January 1992 and September 1997 were recruited into the study, while another 43 age- and sex-matched Chinese patients with type 2 diabetes were recruited as controls. The mean age for the cases was 44.1 years (standard deviation, 11.2 years; median, 42.5 years; range, 20-64 years). The 43 control subjects were age- and sex-matched, and had a mean age of 48.5 years (standard deviation, 10.9 years; median, 51.0 years; range, 16-63 years; P>0.05). The male-to-female ratio was confirmed as similar between the two groups (10:26 versus 12:31; P>0.05). All patients were clinically free from cardiovascular disease. Patients with a history of underlying valvular disease from any cause were excluded from the study. All patients underwent echocardiographic assessment, and the presence of any valvular lesions was documented. RESULTS: The mean duration of dexfenfluramine use by the cases was 21.8 weeks (standard deviation, 29.0 weeks; median, 18.0 weeks; range, 1-160 weeks). Subjects with a history of dexfenfluramine use had higher rates of significant aortic regurgitation, tricuspid regurgitation of any severity, and of any valvular regurgitation, compared to controls (11.1% versus 0%, P<0.05; 30.6% versus 4.7%, P<0.01; and 61.1% versus 34.9%, P<0.05, respectively). Logistic stepwise regression analysis to predict the risk of valvular lesion was conducted, with age, sex, history of dexfenfluramine use, body mass index, waist-hip ratio, blood pressure, fasting plasma glucose, lipid profile, and duration of diabetes as independent variables. A history of dexfenfluramine use was the only significant parameter entered into the model (significant aortic regurgitation: beta=9.19, standard error=46.6, P<0.05; any tricuspid regurgitation: beta=2.76, standard error=10.8, P<0.05). CONCLUSION: In Chinese patients with type 2 diabetes, a history of dexfenfluramine use is associated with heart-valve regurgitation, particularly aortic regurgitation.

Adult↗
PubMed1993

Endocrine and metabolic effects of dexfenfluramine in patients with android obesity.

The effects of dexfenfluramine on 24-hour profiles of ACTH, GH, norepinephrine, insulin and FFA were studied in a group of obese male patients. A controlled comparison trial under metabolic ward conditions was conducted. Dexfenfluramine (15 mg twice daily) was given for 8 days, while patients adhered to a weight maintaining diet. 9 obese patients were treated with dexfenfluramine. 9 obese patients who were randomized on the basis one after another served as a control group. After a 3 day run-in period at 8 am, 10 am, and 4 pm, 8 pm and 12 pm, and 8 am of the following day ACTH, GH, norepinephrine, insulin and FFA were measured before and during the 8th day of dexfenfluramine treatment. During the study body weight slightly decreased in both groups. In the DF group systolic and diastolic blood pressure declined during treatment. The norepinephrine levels were depressed during DF treatment over the entire day. The 24-hour profile of ACTH levels changed in the treatment group to a more distinct circadian rhythm with slightly higher levels in the morning and lower levels at night. The 24-hour profile of GH changed in the drug treated group with a diminished peak of GH secretion at night. Serum concentrations of insulin and FFA were decreased during DF treatment. The hormonal changes during dexfenfluramine treatment suggest that the drug affects endocrine mechanisms that may be involved in regulation of energy balance. Treatment with dexfenfluramine results in decrease of FFA. The mechanisms by which dexfenfluramine operates and displays its various effects on hormones and lipolysis have not been studied.

Adolescent↗
PubMed1994

Acute dexfenfluramine administration normalizes glucose tolerance in rats with insulin-deficient diabetes.

Dexfenfluramine has been shown to lower blood glucose concentrations independently of its effects in reducing food intake and body weight, in human and animal syndromes of non-insulin dependent diabetes. This study aimed to determine whether dexfenfluramine could also reduce glycaemia in rats with severe insulin-deficient diabetes induced by the beta-cell toxin, streptozotocin (55 mg kg-1). Three weeks after diabetes induction, nine groups (each n = 10) of diabetic and non-diabetic rats underwent oral glucose tolerance tests (1 g kg-1, by gavage). These tests were preceded by 12-18 h of fasting to remove the confounding effects of hyperphagia in diabetic rats, and to stabilize glycaemia. Dexfenfluramine (1.0 mg kg-1), given 2 h before the glucose challenge, significantly reduced basal glycaemia and decreased the post-challenge glycaemic rise (P < 0.01 vs. untreated diabetics). Dexfenfluramine dosages of 2.5 and 5.0 mg kg-1 both further flattened the post-challenge glycaemic profiles (both P < 0.01 vs. untreated diabetics) and achieved levels that did not differ significantly from those in non-diabetics (both P > 0.05). Subsequently, the studies using dexfenfluramine dosages of 2.5 and 5.0 mg kg-1 were repeated to determine whether the drug affected plasma insulin levels 2 h after dosing. In diabetic rats, plasma insulin concentrations were reduced to 10-20% of non-diabetic values, and were not significantly altered by dexfenfluramine. Acute dexfenfluramine administration therefore improves and (at dosages of 2.5 and 5.0 mg kg-1) essentially normalizes glucose tolerance in rats with severe insulin-deficient diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Dexfenfluramine. A review of its pharmacological properties and therapeutic potential in obesity.

Dexfenfluramine stimulates serotoninergic activity by inhibiting serotonin reuptake into presynaptic neurons and by enhancing its release into brain synapses. Based on the serotonin hypothesis of appetite control these effects would be expected to reduce food intake and thus body-weight. Studies in animal models and severely overweight patients have confirmed the effectiveness of dexfenfluramine as a weight-reducing agent which appears to be well tolerated. Permanent weight loss is the goal of weight-reducing strategies and, based on current clinical evidence, dexfenfluramine appears to exert a weight reducing effect over periods of up to 12 months without development of tolerance, a problem that has limited the long term use of other pharmacological agents used in the treatment of this disorder. Dexfenfluramine facilitated weight loss in patients who had not responded satisfactorily to other weight-reducing strategies, prevented relapse in those patients who had achieved weight reduction by other methods, and corrected disturbed eating patterns (and therefore reduced weight gain) in small studies involving patients with premenstrual syndrome, seasonal affective disorder and nicotine withdrawal syndrome. Follow-up of the longest study reported with dexfenfluramine suggests that continued therapy is required in severely overweight patients if weight loss is to be maintained. Dexfenfluramine has not been directly compared with nonpharmacological measures of weight control such as behaviour modification or exercise programmes. The decision that pharmacological means are indicated in overweight patients must be highly individualised, and must consider the many complex factors that often contribute to overweight states, as well as the anticipated magnitude of drug effect. Despite such a cautionary note, and the expected need (at this stage of its development) for an expanded clinical study programme in certain areas, dexfenfluramine is a clear advance in the pharmacological approach to improved management of overweight individuals.

Animals↗
PubMed1995

The effect of dexfenfluramine on eating habits in a Dutch ambulatory android overweight population with an overconsumption of snacks.

OBJECTIVE: To investigate the effect of the serotonin receptor agonist dexfenfluramine on eating habits and weight loss in ambulatory, android type, moderately obese patients with an overconsumption of snacks. DESIGN: 9 week, randomized, double-blind treatment with either dexfenfluramine (30 mg/day) or placebo, without dietary intervention. SETTING: Outpatient clinics of four University Hospitals in The Netherlands. SUBJECTS: 112 healthy obese subjects, body mass index 28-35 kg/m2, waist-to-hip ratio > or = 1.0 for men and > or = 0.8 for women, consuming more than five snacks containing in total more than 500 kcal/day and/or more than 25% of total calorie intake in the form of snacks. MAIN OUTCOME MEASURES: Changes in macronutrient composition of the diet, food intake (total, at principal meals and in between meals in the form of snacks) and weight loss. RESULTS: 104 subjects were included for efficacy analysis. In both the dexfenfluramine group (n = 51) and the placebo group (n = 53) the total energy intake decreased. The decrease during main meals was significantly greater in the dexfenfluramine group for all parameters tested except for simple carbohydrates. In between meals the decrease in intake was significantly greater in the dexfenfluramine group for total energy intake (P < 0.05) and intake in unsaturated fat (P < 0.05). The reported reduction in total food intake in the dexfenfluramine group was similarly due to reductions in carbohydrate and fat intake. No weight loss was seen in the placebo group. The treated group lost 3.1 +/- 0.2 kg (P < 0.01). CONCLUSION: Dexfenfluramine effectively reduces the intake of carbohydrates as well as fat in ambulatory, non diet restricted android obese subjects by reducing food intake during and in between main meals.

Adult↗
PubMed1996

Acute and chronic effects of dexfenfluramine on the porcine coronary artery.

Experiments were designed to verify whether or not acute or chronic exposure to dexfenfluramine favors the occurrence of coronary vasospasm in vivo or in vitro. Rings of left anterior and left circumflex porcine coronary artery, with and without endothelium, were studied in conventional organ chambers for the measurement of isometric force. The donor pigs were divided into two groups: controls and animals fed for 4 weeks with dexfenfluramine. In each group, one-half of the animals underwent balloon denudation of the left anterior descending coronary artery at the beginning of the study. Coronary angiography was performed at the time of denudation and, in all animals, during the 3rd week of the study. Acutely, dexfenfluramine at concentrations higher than 10(-5) M caused contractions which were blunted by the presence of the endothelium and inhibited by indomethacin (an inhibitor of cyclooxygenase). Chronic treatment with dexfenfluramine did not affect coronary diameter and did not alter the response to intracoronary infusion of serotonin. Chronic treatment with dexfenfluramine reduced the contractions of rings without endothelium to serotonin, but not those to norepinephrine or endothelin. It did not affect endothelium-dependent relaxations in the absence or presence of pertussis toxin to serotonin, UK14304 (alpha-2 adrenergic agonist), adenosine diphosphate or aggregating platelets. Chronic treatment with dexfenfluramine did not modify relaxations of rings without endothelium to SIN-1 (nitric oxide donor; the active metabolite of molsidomine) or adenosine diphosphate. These findings do not support the hypothesis that acute or chronic exposure to dexfenfluramine favors the occurrence of coronary vasospasm.

Animals↗