Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resting metabolic rate (RMR), as well as caffeine (CAF) and ephedrine (EPH) stimulated thermogenesis (VO2) were measured in young adult corpulent (corp) LA/N-cp (LA-corpulent) rats. RMR of lean was greater than corp. Administration of EPH, CAF and EPH + CAF resulted in 32, 48 and 50% increases in VO2, respectively, in both lean and corp rats. The time to attain maximal VO2 was similar for both drugs in both phenotypes, but the duration of maximal VO2 averaged 50, 26 and 42% longer in corp than lean for EPH, CAF and EPH + CAF, respectively. Acute weight loss following these treatments was greater for corp than lean, and corresponded with the duration of elevated VO2. These results are consistent with a normally functioning end-organ sympathomimetic receptor system in the corp phenotype of the LA/N-cp rat, and suggest that obesity in this model may be caused by factors other than defective brown fat thermogenesis at the end organ level.
 ...
PMID:Caffeine and ephedrine stimulated thermogenesis in LA-corpulent rats. 287 84

To investigate the involvement of adrenergic mechanisms in the development of obesity, hyperglycaemia and hyperinsulinaemia in Aston ob/ob mice, the sympathomimetic agent ephedrine (12 mg/kg/day) and the predominantly beta 1-adrenergic antagonist atenolol (12 mg/kg/day) were administered alone and in combination to weanling ob/ob mice for 40 days. Excessive weight gain in ob/ob mice was reduced (15-20%) by ephedrine, exacerbated (8-10%) by atenolol, but not significantly altered by a combination of these agents. The effects of ephedrine and atenolol were lost rapidly (within 5 days) when these agents were withdrawn. Ephedrine slightly reduced the hyperphagia in ob/ob mice, and food intake was transiently increased above that of untreated ob/ob mice when this agent was withdrawn. The development of basal hyperglycaemia and hyperinsulinaemia was not significantly altered by any of the treatments studied. None of the treatments significantly altered body weight, food intake, plasma glucose or plasma insulin concentrations in lean (+/+) mice. The results indicate that a defective adrenergic mechanism involving beta 1-adrenergic receptors contributes to the development of obesity in ob/ob mice.
 ...
PMID:Effects of ephedrine and atenolol on the development of obesity and diabetes in ob/ob mice. 351 92

The lipolysis in adipose tissue is controlled by the hormone-sensitive lipase activity which is dependent on the intracellular cAMP level. In human adipose tissue, cAMP level is increased by catecholamines (through beta-adrenoceptor stimulation) or decreased by insulin, catecholamine (through alpha 2-adrenoceptor stimulation), neuropeptide Y, prostaglandins and adenosine. The mobilization of lipids from adipose tissue is an adaptative mechanism in response to starvation or hypocaloric diet, which involves reduction of the antilipolytic effect of insulin and the increase of catecholamine sensitivity. The regulatory pathways of lipolysis and their adaptation to caloric reduction are not defective in obesity state. Pharmacological approaches proposed for the activation of lipolysis are limited; they mainly consist either to stimulate the fat cell beta-adrenoceptors (beta-sympathomimetic drugs) or to indirectly activate the sympathetic nervous system (ephedrine and its derivatives, methylxanthines, alpha 2-antagonists). However, the side effects elicited by these drugs frequently limit their clinical use.
 ...
PMID:[Lipid mobilization, physiopathological and pharmacological aspects]. 775 46

The sympathetic nervous system is a major regulator of dietary thermogenesis in laboratory animals and humans. Since a lowered metabolic rate predisposes to the development of obesity, and since caloric restriction suppresses sympathetic activity, a role for adrenergic agonists in the treatment of obesity has a well established physiological rationale. Although diminished sympathetic activity does not appear to underlie obesity in most circumstances in humans, to the extent that adrenergic agonists increase metabolic rate in the obese they may be useful as pharmacologic adjuncts to low energy diets. During caloric restriction the significant diminution in sympathetically mediated thermogenesis antagonizes weight loss; this decrease in metabolic rate may be overcome by sympathomimetic amines thereby increasing the effectiveness of low energy diets. Since smoking stimulates the sympathoadrenal system and increases thermogenesis, smoking cessation, with its attendant fall in sympathoadrenal activity and decrease in metabolic rate, fosters weight gain. Adrenergic agonists may be useful in this circumstance as well.
 ...
PMID:Sympathoadrenal activity and obesity: physiological rationale for the use of adrenergic thermogenic drugs. 838 76

The pivotal role of the sympathoadrenal system in the defense of le milieu interieur has, in the last 15 years, been extended to include the fat stores-a notion that forms the basis of current strategies for thermogenic stimulation in obesity therapy. The search for effective and safe sympathetic stimulants has been directed at two main levels: (i) the development of novel beta-agonists selective for thermogenesis, and (ii) the evaluation of drugs already in clinical use for other purposes (e.g. ephedrine) which could conceivably increase the release of catecholamines to levels that enhance thermogenesis without significant cardiovascular effects. A re-direction of these strategies seem inevitable because at therapeutic doses, the thermogenic effects of these sympathomimetics seem to be considerably dampened by negative feedback mechanisms that operate both extracellularly (e.g. via adenosine & prostaglandins) as well as inside the cells (via cAMP phosphodiesterases). Such a contention is supported by studies both in man and in animals showing that methylxanthines and aspirin, drugs known to be capable of interfering with these modulators, potentiate the thermogenic effects of ephedrine. Future research aimed at clarifying the types and subtypes of these negative modulators of sympathomimetic-induced thermogenesis and their targeting by more selective antagonists would no doubt be pivotal in providing the safe drug combination with the necessary thermogenic properties to assist the management of obesity.
 ...
PMID:Ephedrine, xanthines and prostaglandin-inhibitors: actions and interactions in the stimulation of thermogenesis. 838 78

The sympathoadrenal system plays an important role in the regulation of both energy intake and energy expenditure (EE), and the sympathetic nervous system (SNS) offers a dual target for pharmacological intervention directed at weight loss in obese patients. The sizes of the fat-free mass and fat mass are the major determinants of resting EE, but studies using different techniques have shown that differences in sympathetic activity can account for an additional proportion of the variation between individuals. Differences in thermogenic responses to food can also be explained by different abilities to activate the sympathoadrenal system. A low resting EE for a given body composition is one manifestation of the genetically determined predisposition to obesity. A low sympathetic activity may be one factor responsible but, as yet, no conclusive evidence has been found. In dietary treatment programmes of obesity, patients with high levels of EE and greater SNS activity achieve greater long-term weight loss than those with lower levels. Pharmacological stimulation with sympathomimetic compounds suppresses appetite and increases energy expenditure through stimulation of beta 1, beta 2, and beta 3-receptor subtypes. During chronic treatment, the beta 3-mediation may predominate due to down-regulation of beta 1- and beta 2-receptors. An improved understanding of the aetiological role of the SNS in the development of obesity in genetically susceptible individuals may permit tailoring of pharmacological intervention.
 ...
PMID:The sympathetic nervous system as a target for intervention in obesity. 896 68

1. Carteolol, a non-selective beta-blocker with intrinsic sympathomimetic activity, admixed in a pellet diet was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneous non-insulin-dependent diabetes mellitus with mild obesity. A high dose of carteolol (0.02%) suppressed bodyweight gain without affecting food and water consumption until the appearance of glycosuria. Carteolol tended to reduce the cumulative incidence of glycosuria at 26 weeks after the beginning of administration (55, 17 and 25% in control rats, and in rats fed a low (0.002%) and high dose of carteolol, respectively). 2. At the 26th week of administration, the high dose of carteolol decreased visceral fat weight, such as that of retroperitoneal and epididymal adipose tissue, whereas the liver and the kidney were not affected. 3. Although plasma glucose and triglyceride levels in non-fasted rats were elevated with age, carteolol tended to delay the increases in those parameters. Carteolol suppressed the increase in plasma glucose levels, which indicate the diabetic pattern, in a 25th week oral glucose tolerance test. 4. These findings indicate that carteolol induces improvements in bodyweight and carbohydrate and lipid metabolism in an obese condition. Consequently, carteolol may be useful for the treatment of hypertension with obesity in order to prevent cardiovascular events.
 ...
PMID:Improving effect of carteolol on bodyweight and carbohydrate and lipid metabolic responses in the OLETF rat. 914 81

The pharmacological, deontologic and medico-legal aspects in the use of appetite suppressant drugs have been evaluated. Appetite suppressant drugs used in the treatment of obesity are divided into 2 broad pharmacological categories: those acting via brain catecholamine pathways and those acting via serotonin pathways. Of the former group, amphetamines and phenimetrazines are no longer used because of their stimulant properties and addictive potential. The remaining drugs of this group have some sympathomimetic and stimulant properties. Anorectic drugs which promote serotonin neurotransmission have no such stimulant or sympathomimetic properties. They reduce appetite and food intake and are effective in the treatment of obesity. If they are not used appropriately, appetite suppressants can be of no therapeutic benefit and cause marked health risks. As regards to anorectic drugs, the 13/4/1995 act "Rules and limits in preparing drugs containing anorectic substances", precisely defines rules about selling and use of those substances. Behavior of health care personnel neglecting observance of the rule, could be interpreted as "imprudence", "negligence" and "inexpertness" in designing and managing a fat-reducing diet, that may imply, in case of damage to the patient, a professional fault.
 ...
PMID:[Pharmacological, toxicological, deontologic, and medico-legal aspects of the use of appetite suppressant agents in "weight-loss cures"]. 930 76

Obesity is a multifactorial and complex affectation that is characterized by a long-term excess energy intake (EI) above energy expenditure (EE). Since fat oxidation seems to be dependent on SNS activation and also seems to remain acutely unaffected by fat intake, this macronutrient is certainly partly responsible for this situation. In addition, high-fat intake does not induce as potent satiety signals or a compensation effect on subsequent EI as do diets rich in carbohydrates or proteins. Moreover, since alcohol intake acutely inhibits fat oxidation and does not promote subsequent compensation for its energy content, it should consequently be regarded as a substrate which can induce a positive energy balance under free-living conditions. Thus, in a weight reducing context, each energy substrate should be manipulated while taking into account its specific characteristics. Obesity has also often been associated to a decreased sympathetic nervous system (SNS) activity, hence sympathomimetic agents have been proposed as a possible way to partially correct this situation. Two of these agents are the widely consumed caffeine (CAF) and the pungent principle of hot red pepper, capsaicin (CAP), which acutely increase EE and reduce EI under some circumstances. Furthermore, other factors like dietary fibers, that have been shown to increase satiety and fullness, and reduce EI in some cases, should also be considered.
 ...
PMID:Food intake, energy balance and body weight control. 942 60

Recent clinical trials suggest that resistant hypertension is increasingly common. In the majority of patients, uncontrolled hypertension is due to persistent elevation of the systolic blood pressure. Older age and obesity are associated with poor blood pressure control. Other contributing factors include severity of the underlying hypertension and renal insufficiency. Poor patient adherence is thought be a common cause of medication resistance. Exogenous substances such as nonsteroidal anti-inflammatory drugs, oral contraceptives, and sympathomimetic agents can interfere with treatment. The prevalence of secondary causes of hypertension increases with age, especially atherosclerotic renal artery stenosis. Recent reports suggest that primary aldosteronism may be the most common secondary cause of hypertension. It should be considered in all patients with resistant hypertension. Effective treatment of resistant hypertension requires identification and reversal of contributing factors and/or secondary causes of hypertension. Pharmacologic therapy should utilize combination therapy, including a long-acting diuretic.
 ...
PMID:Resistant hypertension. 1200 5


<< Previous 1 2 3 4 5 Next >>