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

From this review it is obvious that no one pharmacologic agent is universally useful in the treatment of OSA. However, as mentioned in the introductory remarks above, the expectation of beneficial results in a heterogenous population of patients with OSA by specific-acting pharmacologic agents may be somewhat irrational. In addition to this problem, studies performed to date are often not controlled and are usually investigations in small numbers of subjects. However, from the data produced it is apparent that OSA precipitated by endocrinologic problems will improve with hormone replacement. Medroxyprogesterone has been shown to be especially useful in patients with an obesity-hypoventilation component to their disease. Protriptyline may also be useful, but its usefulness is impaired by significant adverse effects. Most likely, both medroxyprogesterone and protriptyline would be more tolerable in female OSA patients, but unfortunately, most of the OSA patient groups studied to date have been composed exclusively of male subjects. Therefore, we do not know if these agents would be more effective and better tolerated in female patients with OSA. The roles of ACE inhibitors and buspirone are not yet established. Serotonin-active agents may be useful in some patients with OSA, but the characteristics of responders are not defined for appropriate patient selection. Much work remains ahead to identify effective pharmacologic agents for OSA. Once identified, these agents must be tested in representative patient groups with a double-blind, placebo-controlled study design in multicenter trials to test the value of these agents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacologic treatment of obstructive sleep apnea. 760 29

The obese Zucker rat is a model of youth-onset obesity associated with hyperphagia. In this study, dehydroepiandrosterone's effect at decreasing food intake and body weight in the obese Zucker rat was investigated. Rats were treated with a dehydroepiandrosterone-supplemented diet (0.0, 0.06, 0.15, 0.3, or 0.6%) for 7 days. The 0.3 and 0.6% treatment groups showed a dramatic decrease in daily food intake, which was evident the 1st day. In addition to the reduction in food intake, body weight changes also were affected significantly in the high-dose treatment groups. The possibility that these dehydroepiandrosterone-induced changes were correlated to perturbations in central neurotransmitter levels associated with appetite control was investigated. The hypothalamus, frontal cortex, striatum, and hippocampus of dehydroepiandrosterone-treated animals were assayed for neurotransmitters known to have inhibitory or stimulatory effects on feeding behavior (serotonin, dopamine, norepinephrine, and epinephrine). Significant differences from steroid-free controls were noted only in the levels of hypothalamic serotonin in animals treated with dehydroepiandrosterone. Serotonin in the hypothalamus has been shown to decrease feeding behavior. The magnitude of dehydroepiandrosterone's effect on hypothalamic serotonin correlated with its effect on feeding behavior. Thus, dehydroepiandrosterone may reduce hyperphagia by altering hypothalamic levels of serotonin.
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PMID:Effect of dehydroepiandrosterone on neurotransmitter levels and appetite regulation of the obese Zucker rat. The Obesity Research Program. 768 87

To clarify neuronal disturbance in the hypothalamus reflecting the development of obesity in ventromedial hypothalamic nucleus (VMH)-lesioned rats, we investigated the contents of neurotransmitters in the hypothalamus after pretreatment by microwave irradiation, contents of neurotransmitter metabolites in third ventricle fluid and catecholamine contents in the adrenal gland. The hypothalamic contents of norepinephrine (NE) and dopamine (DA) were selectively decreased, but acetylcholine (ACh) and serotonin (5-HT) levels were not changed from those in controls. In the lateral part of the hypothalamus, also, a significant decrease of NE content was detected. On the other hand, NE and DA metabolites, MHPG, DOPAC and HVA were increased in the third ventricle fluid in VMH lesion-induced obese rats. Wet weight and content of epinephrine in the adrenal gland were decreased, though the content of NE was preserved. These results indicate that a disturbance of NE and DA neurons in the hypothalamus is involved in the development of VMH lesion-induced obesity. In addition, an increment of the activities of NE and DA systems in the central nervous system as a whole and some irregularity in the sympatho-adrenal system might contribute to VMH obesity.
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PMID:Aspects of hypothalamic neuronal systems in VMH lesion-induced obese rats. 796 56

There are two mechanisms leading to an enhancement of salt intake: one is induced by a sodium deficit and the other is need-free. The serotonin involvement in need-induced and/or need-free sodium appetite is interesting to consider because related drugs are already used against another cardiovascular risk factor, obesity. The effect of dexfenfluramine (1.5 or 3 mg/kg), an anorectic drug enhancing 5-HT transmission, and of metergoline (2 or 4 mg/kg), a 5-HT antagonist, was assessed in need-induced (depletion-induced), subsequent need-free, and spontaneous sodium appetite. Dexfenfluramine (3 mg/kg) decreased by 75% to 90% the depletion-induced intake of an aversive 3% NaCl solution, as well as the spontaneous intake of a less aversive 1.8% NaCl solution. Water intake was not diminished under these conditions. Metergoline significantly increased salt intake in need-free conditions in rats with either a history of three previous depletions or not. These results confirm the involvement of serotonin in sodium appetite and extend this involvement to both need-induced (natriorexis) and need-free (natriophilia) conditions. The metergoline experiments also suggest that 5-HT exerts a tonic inhibition on salt intake.
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PMID:Serotoninergic modulation of sodium appetite in the rat. 802 98

Genetically obese (ob/ob) and lean C57BL/6J mice were subjected to 1 h acute restraint stress, and the effects on plasma glucose and corticosterone, and brain amines, were assessed relative to nonrestrained groups. Some mice were treated with dexfenfluramine (DFEN) prior to restraint. Compared with their lean counterparts, ob/ob mice had elevated basal plasma levels of both glucose and corticosterone. Both lean and ob/ob showed comparable absolute restraint-induced increments in these measures, but the fractional increase was much smaller in ob/ob. Metabolism of NE, DA and 5-HT was also assessed from the ratio of the metabolite-to-amine in various brain regions. Obese mice had smaller restraint-related increases in monoamine metabolism than lean their counterparts. Acute DFEN increased corticosterone, but tended to reduce the restraint-induced elevations in glucose and monoamine metabolism.
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PMID:Effect of dexfenfluramine on metabolic and neurochemical measures in restraint-stressed ob/ob mice. 855 86

The association between insulin resistance, obesity, and hypertension is well recognised. We examined the hypothesis that hypertension in the obese Zucker rat is related to changes in vascular reactivity. Systolic blood pressure (SBP) in conscious Zucker rats was significantly greater in obese as compared with lean animals (157 +/- 9 and 117 +/- 8 mm Hg). Obese animals also had marked proteinuria and reduced urinary creatinine excretion in 24 h as compared with their lean counterparts. The reactivity of isolated aorta to phenylephrine (PE) and 5-hydroxy-tryptamine (5-HT) was modestly (twofold) increased in obese animals (EC50 13.8 nM as compared with 29.4 nM in lean animals and 0.19 nM as compared with 0.46 nM in lean animals, respectively). In the perfused mesenteric vascular bed, basal perfusion pressure was the same in both phenotypes, as was the pressor response to PE and depressor response to acetylcholine (ACh) and sodium nitroprusside (SNP). In the isolated aorta, from obese animals, insulin attenuated the contractile response to PE but markedly enhanced the vasoconstrictor potency of 5-HT. It had no significant effect on pressor or depressor responses in the perfused mesenteric bed. The data suggest that increased reactivity of central arteries to spasmogenic agents may be involved in the development of systolic hypertension in the hyperinsulinaemic Zucker rat.
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PMID:Effects of genetic hyperinsulinaemia on vascular reactivity, blood pressure, and renal structure in the Zucker rat. 863 85

We have shown previously that intravenous infusions of insulin, known to induce glucoprivic hunger, and of insulin combined with glucose, known to induce satiety, produce in the VMH and PVN of Wistar rats monoaminergic changes that differ from those related to spontaneously occurring hunger and satiety, while the genetically obese Zucker rat is totally resistant to the behavioural effects of insulin and insulin + glucose infusions. In the present study, the impact of these infusions on VMH and PVN monoamines in obese Zucker rats was assessed using microdialysis. Monaminergic changes (increase in DOPAC and 5-HIAA and decrease in DA and 5-HT) were quite similar in obese rats to those we found in normal rats when insulin was infused. In contrast, changes in 5-HT or DA in response to insulin and glucose were quite different in the Zucker rat. Monoaminergic changes related to meals were more dramatic in the Zucker rat and so were able to reverse the background changes produced by the insulin infusion. These data confirm the idea that the effect on monoamines of spontaneously occurring hunger and satiety is different from the effect on monoamines by insulin and glucose-induced hunger and satiety. The results show disturbances of the obese Zucker rat related both to insulin and to hypothalamic monoamines that may be involved in the hyperphagia and obesity of this model.
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PMID:Rostromedial hypothalamic monoamine changes in response to intravenous infusions of insulin and glucose in freely feeding obese Zucker rats: a microdialysis study. 866 29

Recent progress in the molecular pharmacology of 5-HT receptors and the development of selective ligands for various 5-HT receptor subtypes has advanced our understanding of the role of 5-HT mechanisms in the control of food intake and bodyweight. The most intensively investigated 5-HT receptor subtypes have been the 5-HT1A receptor, the 5-HT1B receptor and the 5-HT2C receptor. The overall pattern of results to date suggests that selective 5-HT2C agonists may be novel anorectic drugs and prove useful in the treatment of obesity. However, a number of issues remain unresolved, particularly regarding potential side-effects, as the 5-HT2C receptor agonist mCPP has been reported to induce anxiety and nausea in humans, actions that would clearly limit its therapeutic utility. In addition, the possible role of recently cloned 5-HT receptor subtypes such as 5-ht5, 5-ht6 and 5-ht7, remains unexplored and the development of selective ligands for these sites has the potential to lead to new treatments for obesity.
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PMID:Multiple serotonin receptors: opportunities for new treatments for obesity? 869 43

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

A number of drugs are capable of changing bodyweight as an adverse effect of their therapeutic action. Bodyweight gain is more of a problem than bodyweight loss. As bodyweight gain during drug treatment for any kind of disease may be the reflection of improvement of the disease itself, we will try to separate these effects from those due to drug-induced alterations of the mechanisms regulating bodyweight. Bodyweight gain may jeopardise patient compliance to the prescribed regimen and it may pose health risks. The body mass index (BMI) is determined by dividing bodyweight in kilograms by height in metres squared. A BMI of > or = 27 kg/m2 warrants therapeutic action; nutritional counselling and programmed physical exercise can be used as a basis. In general, if basic therapeutic measures are unsuccessful at controlling bodyweight gain then a change of drug might help. Finally, an anoretic drug may serve to support dietary measures. However, safety and efficacy has been demonstrated for only a few anorectic drugs when used as an adjunct to caloric restriction in the treatment of drug-induced obesity. Bodyweight is determined by complex mechanisms regulating energy balance. A number of neurotransmitter systems acting in several hypothalamic nuclei are pivotal to the regulation of body fat stores. Most drugs that are capable of changing bodyweight interfere with these neurotransmitter systems. The increment is dependent on the type and dose of the drug concerned. Some antidepressant drugs induce bodyweight gain, which may amount to 20 kg over several months of treatment. Monoamine oxidase inhibitors appear to cause less bodyweight change than tricyclic antidepressants. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors cause bodyweight loss instead of bodyweight gain. Lithium may cause large increases in bodyweight. Generally speaking, the bodyweight change induced by antipsychotics is more often of clinical significance than the bodyweight change associated with the use of antidepressants. Again, the changes of bodyweight are dependent upon the type and dose of the antipsychotic drug involved. Although almost all antipsychotics induce bodyweight gain, molindone and loxapine appear to induce bodyweight loss. Anticonvulsants, especially valproic acid (sodium valproate) and carbamazepine, induce bodyweight gain in a considerable percentage of patients. Treatment with corticosteroids is associated with dose-dependent bodyweight gain in many patients. Corticosteroid-induced obesity aggravates other corticosteroid-associated health risks. Insulin therapy in diabetic patients usually increases bodyweight. Finally, sulphonurea derivatives, antineoplastic agents used for the treatment of breast cancer and several drugs used in migraine prophylaxis may cause bodyweight gain as well.
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PMID:Bodyweight change as an adverse effect of drug treatment. Mechanisms and management. 880 Jun 28


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