Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventeen hyperkinetic children who had previously responded to sympathomimetic amines were given three different dosages of caffeine in counterbalanced order (placebo, and low and high doses equivalent to one and three cups of coffee). One hour following ingestions they were tested, double-blind on measures of visual evoked response, alpha time, vigilance, and activity level. There was a significant effect on evoked response. The behavioral measures tended to be affected in a dose-related manner but not to a statistically significant degree. It is concluded that although centrally active, caffeine does not show the congruence between behavioral and central effects that other stimulants useful in behavioral management have shown.
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PMID:The acute effects of caffeine on evoked response, vigilance, and activity level in hyperkinetic children. 46 8

The sympathomimetic agent ephedrine has potent thermogenic and anti-obesity properties in rodents. The effect is markedly enhanced by caffeine, while caffeine given alone has no effect. This study was undertaken to find out if a similar weight reducing synergism between ephedrine and caffeine is present in obese patients. In a randomized, placebo-controlled, double blind study, 180 obese patients were treated by diet (4.2 MJ/day) and either an ephedrine/caffeine combination (20mg/200mg), ephedrine (20 mg), caffeine (200 mg) or placebo three times a day for 24 weeks. Withdrawals were distributed equally in the four groups, and 141 patients completed the trial. Mean weight losses was significantly greater with the combination than with placebo from week 8 to week 24 (ephedrine/caffeine, 16.6 +/- 6.8 kg vs. placebo, 13.2 +/- 6.6 kg (mean +/- s.d.), P = 0.0015). Weight loss in both the ephedrine and the caffeine groups was similar to that of the placebo group. Side effects (tremor, insomnia and dizziness) were transient and after eight weeks of treatment they had reached placebo levels. Systolic and diastolic blood pressure fell similarly in all four groups. We conclude, that in analogy with animal studies, the ephedrine/caffeine combination is effective, while caffeine and ephedrine separately are ineffective for the treatment of human obesity.
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PMID:The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double blind trial. 131 81

Current concepts about the mechanisms underlying the therapeutic effects of dietary methylxanthines (caffeine, theophylline, and theobromine) favor their actions as antagonists of adenosine receptors, and attribute their other possible modes of action, namely those associated with translocation of intracellular calcium, inhibition of phosphodiesterase enzyme (PDE) activity, or the release of catecholamines, to high (near-toxic) doses. From studies measuring the respiration rate of brown adipose tissue (BAT), evidence is provided here that at concentrations compatible with therapeutic doses, the ability of methylxanthines (25 to 50 mumol/L) to potentiate the thermogenic effect of the sympathomimetic drug, ephedrine (0.25 mumol/L), particularly under conditions of caloric restriction, involves a minor contribution of adenosine antagonism, but could mainly be explained by the inhibition of PDE activity. In view of current interest in the pharmacological stimulation of metabolic rate to assist the management of obesity with low-calorie regimens, the targeting of PDE activity is therefore a rational approach in the search for drugs that could potentiate sympathomimetic stimulation of metabolic rate.
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PMID:Potentiation of the thermogenic antiobesity effects of ephedrine by dietary methylxanthines: adenosine antagonism or phosphodiesterase inhibition? 143 97

Adipsin gene expression is severely diminished in certain forms of genetic and acquired rodent obesity. Common to many of these models of obesity is decreased sympathetic nervous system (SNS) activity. In addition, treatment of MSG obese mice with the sympathomimetic drug mixture ephedrine and caffeine restores adipsin deficiency to normal, while reversing obesity. Based on these observations, we hypothesized that adipsin gene expression might be regulated through changes in SNS activity with deficient adipsin gene expression in obesity being the result of impaired SNS activity. In the present study we used three models to assess the role of the SNS in regulating adipsin gene expression. First we exposed mice to the cold (4 degrees C), a potent activator of SNS activity. Second, we chemically sympathectomized mice with 60H-dopamine. Third, we treated mice with BRL 26830A, an atypical beta adrenoreceptor agonist. In contrast to our initial hypothesis, these studies demonstrate that alterations of SNS activity do not affect adipsin gene expression in normal mice. Neither increased SNS activity secondary to cold exposure nor decreased SNS activity resulting from sympathectomy alter serum adipsin concentration or adipsin mRNA levels in white (WAT) and brown adipose tissue (BAT). Surprisingly, treatment of lean mice with BRL 26830A decreases both adipsin serum concentrations and adipsin mRNA levels, suggesting a potential role for atypical beta adrenoreceptors in pathways that suppress adipsin expression in vivo. The significance of this observation with respect to adipocyte physiology is unclear at present. Future studies will be aimed at defining the molecular mechanisms by which BRL 26830A suppresses adipsin gene expression and the physiological significance of this effect.
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PMID:Alterations in sympathetic nervous system activity do not regulate adipsin gene expression in mice. 164 81

Drug use among athletes has become a recognised problem in sports. Athletes may use drugs for therapeutic indications, for recreational or social reasons, as ergogenic aids or to mask the presence of other drugs during drug testing. Stimulants were some of the first drugs used and studied as ergogenic aids. Amphetamines may increase time to exhaustion by masking the physiological response to fatigue. Caffeine may improve utilisation of fatty acids as a fuel source thereby sparing muscle glycogen. Cocaine and other sympathomimetic drugs have little or no effect on athletic performance. Anabolic steroids appear to have the potential to increase lean muscle mass and strength under certain conditions. Human growth hormone may also be used for an anabolic effect, but data on this effect are lacking. Erythropoietin may represent a pharmacological alternative to blood doping by increasing red blood cell mass. The use of narcotic analgesics is not necessarily ergogenic but can be harmful if used to allow participation of an athlete with a severe injury. According to the American College of Sports Medicine alcohol does not possess an ergogenic effect. However, it may be used to reduce anxiety or tremor prior to competition. Marijuana does not increase strength. Tobacco products may produce psychomotor effects or control appetite which may be beneficial to some athletes. Other drugs used by athletes include beta-blocking agents, diuretics, and a variety of nutritional supplements. In addition, diuretics and probenecid may be taken to mask drug contents in the urine. Whether the ergogenic effects are real or perceived, the potential for adverse effects exists for all of these drugs. Potential health complications represent a serious risk to an otherwise healthy population. Further research on the long term health risks in athletes taking ergogenic drugs is needed.
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PMID:Enhancement of athletic performance with drugs. An overview. 168 20

Phenylpropanolamine, a widely consumed over-the-counter drug, is known to elevate blood pressure, but the mechanism is unknown; it may be both a direct and indirect sympathomimetic. This study investigated the effects of 75-mg sustained-release phenylpropanolamine, 75-mg phenylpropanolamine plus 400-mg caffeine, and 150-mg phenylpropanolamine on blood pressure, plasma norepinephrine, and epinephrine levels in 16 normotensive subjects in a double-blind, placebo-controlled crossover design. Mean peak phenylpropanolamine levels of 317 +/- 26, 152 +/- 17, and 157 +/- 17 ng/mL for 150-mg phenylpropanolamine, 75-mg phenylpropanolamine, and 75-mg phenylpropanolamine plus 400-mg caffeine, respectively, were reached at about 3.6 hours after dosing. The maximal increases in supine diastolic blood pressures after all three phenylpropanolamine-containing drugs were almost three times that after placebo (P less than .05), but peak blood pressures occurred at about 2.3 hours earlier than peak phenylpropanolamine levels. Blood pressure increases correlated with phenylpropanolamine plasma levels (r = .49 for systolic blood pressure and r = .34 for diastolic blood pressure; P less than .0001 for both). Norepinephrine levels increased after the administration of 150-mg phenylpropanolamine and 75-mg phenylpropanolamine plus 400-mg caffeine; norepinephrine increases correlated with phenylpropanolamine levels (r = .34, P less than .0001). The expected increment in norepinephrine induced by standing was significantly decreased by phenylpropanolamine in a dose-dependent mode. The study supports the idea that phenylpropanolamine as both a direct (at alpha -1 and alpha-2 receptors) and an indirect sympathomimetic agent.
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PMID:Dose-dependent response to phenylpropanolamine: inhibition of orthostasis. 189 58

We surveyed phenylpropanolamine (PPA) use and overuse among 309 diet center clients. Fifty-one percent of all subjects surveyed reported using PPA drugs: 44 percent used cold medicines and 16 percent used diet aids. Twenty-two percent of diet aid users and 7 percent of cold medicine users reported that they deliberately used more than the dosage recommended to improve efficacy. Among diet aid users, 59 percent also regularly consumed caffeine. Despite package warnings, individuals who had been told by their doctors that they were hypertensive used PPA products as often as normotensive individuals. PPA, the fifth most frequently used drug in the USA, is contained in over-the-counter (OTC) diet aids as well as OTC and prescription cold medicines. Severe adverse drug reactions (ADRs) including hypertensive crisis, stroke and death have been attributed to PPA products. Clinical studies have shown that using greater than recommended doses of PPA and using PPA in combination with caffeine may increase the risk of ADRs. Overweight patients may be particularly at risk for ADRs to PPA because they are likely to be hypertensive and to use diet aids. We recommend informing diet center clients of the potential dangers of consuming PPA products, especially more than the recommended dose, in the presence of hypertension, and when other sympathomimetic drugs are being taken.
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PMID:Phenylpropanolamine and caffeine use among diet center clients. 222 92

Adipsin gene expression is greatly diminished in certain forms of genetic and acquired obesity. In the present study we evaluate the time course for the development of adipsin deficiency in obesity and its regulation by the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. Previously, it was unknown whether adipsin deficiency occurred before or after the development of massive obesity. In the first series of experiments in which mice were treated with monosodium glutamate (MSG) for the first week of life, we demonstrate that adipsin deficiency occurs early in the development of MSG-induced obesity as evidenced by decreased circulating adipsin concentrations by 1 week of age and deficient adipsin mRNA levels in white adipose tissue (WAT) by 2 weeks. In db/db mice, diminished circulating adipsin was noted at 2 weeks of age. In both models, decreased adipsin gene expression precedes the development of marked obesity. Little is known about the factors which regulate adipsin gene expression in obesity. Common to the ob/ob, db/db and MSG models is diminished thermogenesis and sympathetic nervous system activity. In a second series of experiments we sought to determine whether adipsin deficiency in obesity could be corrected by treatment with ephedrine and caffeine (E+C), a sympathomimetic-thermogenic mixture previously shown to increase thermogenesis and reverse obesity in some models. In the present study, E+C treatment of MSG obese mice reversed obesity and markedly increased serum adipsin and adipsin mRNA levels in WAT and brown adipose tissue (BAT). In ob/ob mice, however, E+C treatment produced a negligible increase in adipsin mRNA levels in WAT and BAT as well as serum adipsin concentrations and this correlated with only a very small decrease in obesity. Thus, the ability of E+C to increase adipsin gene expression correlated with its ability to reverse obesity in these two models. Finally, the effect of E+C on adipsin gene expression may not be exerted directly on the fat cell since treatment of cultured 3T3-F442A adipocytes and isolated rat adipocytes in primary culture produced no effect on adipsin mRNA or secreted protein despite a lipolytic effect as measured by increased glycerol release. In summary, decreased adipsin gene expression occurs early in the development of MSG and db/db obesity and is markedly increased in the MSG model by the sympathomimetic-thermogenic drug mixture, E+C, which also reverses obesity. Elucidation of the factors responsible for these effects may enhance our understanding of fat cell gene regulation and obesity.
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PMID:Reduced adipsin expression in murine obesity: effect of age and treatment with the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. 230 16

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.
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PMID:Caffeine and ephedrine stimulated thermogenesis in LA-corpulent rats. 287 84

We showed previously that circulating adenosine potentiates pressor responses to nicotine in rats, apparently by enhancing the effects of nicotine in sympathetic ganglia. In the present studies, we examined the effects of adenosine (or synthetic adenosine receptor agonists) on a variety of sympathomimetic responses to nicotine (or other nicotinic cholinergic agonists). Indices of sympathetic activity examined were: blood pressure; heart rate; eyelid tension; and vas deferens perfusion pressure. Elevation of arterial plasma adenosine from its basal level (approximately 1.5 microM) to 2 to 3 microM (by i.v. adenosine infusion) had no effect on the basal value of any of these indices, but increased by 2.5 to 4-fold their peak responses to nicotine (40 microgram/kg i.v.). Adenosine also strongly enhanced sympathomimetic responses to inhaled cigarette smoke. The adenosine receptor antagonist caffeine (10 mg/kg) suppressed the ability of adenosine to potentiate these responses to nicotine. Pressor responses to the nicotinic cholinergic receptor agonists dimethylphenylpiperazinium iodide, tetramethylammonium, lobeline and cytisin were also potentiated by adenosine. Low doses (0.25-5 mu/kg) of synthetic adenosine receptor agonists potentiated all four of the tested sympathomimetic responses to nicotine, exhibiting the rank order of potency: N-Cyclopropylcarboxamidoadenosine greater than 2-Chloroadenosine greater than N6-R-Phenylisopropyl adenosine greater than N6-S-Phenylisopropyladenosine. The nonpurinergic vasodilator sodium nitroprusside failed to potentiate responses to nicotine, suggesting that the influence of adenosine on responses to nicotine is not secondary to its direct circulatory effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine potentiates sympathomimetic effects of nicotinic agonists in vivo. 300 40


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