Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Desipramine and fenfluramine were administered to bulimic patients in a 15-week study of double-blind, placebo-controlled, crossover design. The 22 patients in the study met DSM-III criteria for bulimia and were of normal weight. Twelve subjects were randomly allocated to the fenfluramine group, and 10 subjects received desipramine. Half the subjects in each group received the active drug in the first 6 weeks and half received placebo. There was a 3-week washout period, after which subjects were crossed over for the remaining 6 weeks. The Eating Disorder Inventory, profile of Mood States, bulimia symptom checklists, and Hopkins Symptom Checklist were administered at weeks 0, 2, 4, 6, 9, 11, 13, and 15. Subjects maintained a daily record of bingeing, vomiting, and laxative/diuretic abuse. Results indicated that both drugs had beneficial effects on bingeing and vomiting frequency, although a greater proportion of patients were identified who responded to fenfluramine than to desipramine. Fenfluramine and desipramine were also effective in reducing the psychological symptoms of bulimia, such as the urge to binge, and feelings of depression. Results suggest that direct alteration of central food intake regulatory centers can effectively control bulimia.
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PMID:Treatment of bulimia with fenfluramine and desipramine. 306 43

Fenfluramine (Fen) 40 mg, a selective releaser of serotonin, and dextroamphetamine (Dex) 15 mg were administered in a double-blind crossover design to 16 subjects with major affective disorder, depression. Three hours after administration both drugs significantly improved depression and improved vigor, fatigue, and confusion-bewilderment on the subscales of the Profile of Mood States. Dex was significantly better than Fen only on the vigor and fatigue subscales. Other data from this study suggest that when used acutely Fen can mimic long-term antidepressant effects, whereas the acute effects of Dex are similar to its stimulating effects in normals.
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PMID:A comparison of the acute effects of dextroamphetamine and fenfluramine in depression. 389 98

In order to investigate the effect of fenfluramine on hormonal and metabolic changes with exercise, five normal volunteers have been studied during and after 20 minutes of steady exercise on a bicycle ergometer after injection of fenfluramine (20 mg intravenously). Fenfluramine abolished the rise of plasma human growth hormone (HGH) which occurred in control investigations. Fenfluramine also affected plasma insulin, blood glucose, and ketone body levels.The acute effect of fenfluramine on the release of growth hormone was examined further by studying its effect in patients with acromegaly. A marked depression of growth hormone occurred both at rest and with exercise. These observations indicate that fenfluramine has a direct effect on pathways controlling growth hormone release. We also suggest that this action may have practical use in the medical treatment of acromegaly.
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PMID:Effect of fenfluramine on human growth hormone release. 470 18

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

In an attempt to evaluate the responsiveness of the serotonergic neurotransmitter system in depression, fenfluramine, a serotonin releasing agent, was administered to 18 depressed patients and 10 controls, and placebo was administered to 16 of the depressed patients in a double-blind paradigm. Plasma prolactin levels were measured prior to and for five hours following fenfluramine. Fenfluramine produced a significant increase in prolactin in both patients and controls. However, the prolactin response to fenfluramine whether measured as an absolute increase or percent increase from baseline was significantly less in depressed patients than controls. This difference remained equally statistically significant when age-and-sex-matched pairs of depressed patients and controls were compared. These results suggest that the central serotonergic system is less responsive in depressed patients than controls.
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PMID:Plasma prolactin changes following fenfluramine in depressed patients compared to controls: an evaluation of central serotonergic responsivity in depression. 670 Mar 67

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

d-Fenfluramine, a specific 5-HT releasing agent without the catecholamine effects of d,l-fenfluramine, was used as a serotonergic neuroendocrine challenge in subjects with unipolar major depression. Prolactin and cortisol responses to 30 mg d-fenfluramine were measured in patients at baseline. Patients were then randomly assigned to treatment for 6 weeks with a specific noradrenergic reuptake inhibitor, a tricyclic antidepressant, or placebo. Response to antidepressant treatment was assessed, and patients underwent further testing with d-fenfluramine. Prolactin responses were increased by treatment, but this was independent of whether or not patients' depression responded to treatment. Seven patients were treated with a specific noradrenergic reuptake inhibitor. These patients showed a significant rise in 5-HT-mediated cortisol responses after treatment, independent of whether their depression improved. We conclude that antidepressants which selectively modify noradrenergic function also have effects on 5-HT function as measured by neuroendocrine testing.
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PMID:Do noradrenergic reuptake inhibitors affect serotonergic function in depression? 945 84

1. The entorhinal cortex (EC), main input structure to the hippocampus, gets innervated by serotonergic terminals from the raphe nuclei and expresses 5-HT-receptors at high density. Using extra- and intracellular recording techniques we here investigated the effects of serotonin on population and cellular responses within the EC. 2. Stimulation in the lateral entorhinal cortex resulted in complex field potential responses in the superficial EC. The potentials are composed of an early antidromic and a late orthodromic component reflecting the efferent and afferent circuitry. 3. Serotonin (5-HT) reduced synaptic potentials of the stimulus evoked extracellular field potential at all concentrations tested (0. 1 - 100 microM; 59%-depression by 10 microM serotonin), while the antidromic response was not significantly changed by up to 50 microM 5-HT. Depression of field potential responses by serotonin was associated with a significant increase in paired-pulse facilitation from 1.15 to 1.88. 4. The effects of serotonin on field potential responses were mimicked by 5-HT1A-receptor agonists (8-OH-DPAT, 5-CT) and partially prevented by the 5-HT1A-receptor antagonist (S-UH-301). Moreover, the 5-HT1A-receptor antagonist WAY100635 reduced the effect of 5-CT. 5. Fenfluramine, a serotonin releaser, mimics the effects of serotonin on stimulus-evoked field potential responses, indicating that synaptically released serotonin can produce the changes in reactivity to afferent stimulation. 6. Depression of isolated AMPA-receptor mediated EPSCs by serotonin as well as fenfluramine was associated with an increase in paired pulse facilitation, indicating a presynaptic locus of action. 7. We conclude that physiological concentrations of serotonin potently suppresses excitatory synaptic transmission in the superficial entorhinal cortex by a presynaptic mechanism.
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PMID:Potent depression of stimulus evoked field potential responses in the medial entorhinal cortex by serotonin. 1049 59

The olfactory bulbectomized (OBX) rat is an animal model of depression with neurochemical, neuroendocrinological and behavioral features resembling some human depression. d-Fenfluramine is a 5-HT releasing drug, frequently used in the study of the responsivity of the 5-HT system in subjects with psychiatric disorders, including depression. The aim of the study is to assess the influence of the serotonin-releaser, d-fenfluramine, in the OBX rat model of depression, as measured by the change in the regional cerebral glucose utilization rCGU) following d-fenfluramine injection. Male Sprague-Dawley rats (160-180 g) were used. The rats were divided into OBX and Sham groups. Two weeks following the olfactory bulbectomy or the sham surgery, six rats (randomly assigned) from each group received an i.p. injection of d-fenfluramine with a dose of 5 mg/kg or the same volume of saline. Twenty minutes later, the rCGU rates were measured using 2-[(14)C]deoxyglucose autoradiography. The general linear model statistical analysis has shown that the rCGU in the sham-operated rats treated with d-fenfluramine, compared to the sham-operated rats treated with saline, was lower in 14 (36%) out of 39 examined brain regions. There was no significant difference in the rCGU between the OBX rats treated with d-fenfluramine and OBX rats treated with saline. The results suggest the blunted capacity of the 5-HT system in OBX rats to respond to the challenge by the 5-HT releasing compound, d-fenfluramine. This resembles similar findings in clinical studies on depressed patients.
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PMID:Acute challenge with d-fenfluramine decreases regional cerebral glucose utilization in Sham, but not in OBX, rats: an autoradiographic study. 1991 94

The prevalence of obesity increases and is associated with increases in co-morbidities e.g. type 2 diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, heart disease, stroke, asthma, several forms of cancer, depression, and may result in reduction of expected remaining lifespan. We have reviewed the adverse effects on the cardiovascular system of anti-obesity drugs now retracted from the market as well as the cardiovascular profile of current drugs and potential pathways which are considered for treatment of obesity. Fenfluramine, and sibutramine were withdrawn due to increased cardiovascular risk, while an inverse agonist at cannabinoid type 1 (CB1) receptors, rimonobant was withdrawn due to serious psychiatric problems. At present there are only few treatments available including orlistat and, phentermine alone or in combination with topiramate and lorcaserin, although cardiovascular side effects need to be clarified regarding phentermine and lorcaserin. Drugs approved for type 2 diabetes including glucagon like peptide (GLP-1) analogues and metformin also cause moderate weight losses and have a favourable cardiovascular profile, while the anti-obesity potential of nebivolol remains unexplored. Pathways with anti-obesity potential include sirtuin activation, blockade of transient receptor potential (TRPV1) channels, acetyl-CoA carboxylase 1 and 2 inhibitors, uncoupling protein activators, bile acids, crotonins, CB1 antagonists, but the cardiovascular profile remains to be investigated. For type 2 diabetes, new drug classes with possible advantageous cardiovascular profiles, e.g. GLP-1 analogues and sodium-glucose co-transport type 2 inhibitors, are associated with weight loss and are currently being evaluated as anti-obesity drugs.
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PMID:Cardiovascular effects of current and future anti-obesity drugs. 2484 38


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