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

1 The sympathetic noradrenergic activation of brown adipose tissue and the biochemical mechanisms involved in diet-induced thermogenesis were studied in rats. 2 A close correlation was found between brown adipose tissue Na+, K+-adenosinetriphosphatase (Na+, K+-ATPase) activity in vitro and in vivo measurements of resting oxygen consumption (VO2). The effects of noradrenaline on in vitro NA+, K+-ATPase activity in brown adipose tissue and in vivo VO2 could be mimicked by a variety of agents. These included beta-adrenoceptor agonists and agents known to induce the release of noradrenaline or inhibit the noradrenaline uptake process. The pharmacological evidence suggests that dopaminergic mechanisms may also be involved in the control of thermogenesis. 3 Amphetamine did not increase VO2 in rats without causing associated increases in locomotor activity. Ciclazindol at doses of 3-30 mg/kg intraperitoneally increased VO2 but did not appear to increase locomotor activity or evoke any other signs of CNS stimulation including lengthening of time to sleep onset or stereotypy. Separation of metabolic and CNS effects occurred only at the lowest dose of mazindol used (0.3 mg/kg i.p.). These results are probably a reflection of (a) the relative abilities of these drugs to inhibit brain and brown adipose noradrenaline uptake processes and (b) the relatively high accumulation of ciclazindol in brown adipose. 4 Of the drugs tested, only ciclazindol was a more potent inhibitor of the noradrenaline uptake system in brown adipose tissue (BAT) than in brain. Kinetic analysis also revealed that the actions of ciclazindol on the NA uptake system and Na+, K+-ATPase in BAT differed from those of mazindol. 5 These findings suggest that ciclazindol may produce an energy wasting effect in rodents without causing overt CNS stimulation; the implications of these findings in terms of human obesity are discussed.
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PMID:Sympathetic mechanisms in diet-induced thermogenesis: modification by ciclazindol and anorectic drugs. 627 18

Ciclazindol, a noradrenaline (NA) uptake inhibitor originally introduced as an antidepressant, has recently been shown to produce weight loss in experimental animals and patients. Unlike CNS-stimulant anti-obesity drugs, such as amphetamine, ciclazindol may induce weight loss in animals by stimulating thermogenesis in brown adipose tissue (BAT), and it is known to stimulate resting metabolic rate (RMR) of rats and depress energetic efficiency. These effects can be achieved in the absence of overt CNS stimulation and with certain analogues of ciclazindol may be due to an exclusive peripheral action. Mazindol, a structural analogue of ciclazindol also produces an increase in RMR. However the increment is qualitatively and quantitatively different from that observed with ciclazindol and cannot be dissociated from central stimulant actions. In this report we examine some of the physiological and behavioural effects of ciclazindol and mazindol analogues in rats.
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PMID:Thermogenic properties of ciclazindol and mazindol in rodents. 653 97