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)

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

The effects of mazindol on the salivary secretion of dogs was investigated. Mazindol (2 mg/kg, i.v.) decreased the volume and pressure of salivary secretion induced by either chemical (carpronium) stimulation or electrical nerve stimulation. It also reduced spontaneous salivary secretion. Secretion velocity in the mazindol treated group was significantly less than in the physiological saline administered control group at 4 to 6 min after injection. Saline and mazindol produced no significance differences in Na+, Cl- or K+ concentrations in the saliva or serum. Thus mazindol inhibition of salivary secretion was not caused by ion transport. The existence of some other inhibitory mechanism is suggested. The effects of mazindol on the peripheral and central control of gastric acid secretion was also investigated in rats. Gastric acid secretion induced by direct application of cholinergic agents on oxyntic cells was not affected by mazindol. Gastric acid secretion induced by insulin and/or 2-DG, on the other hand, was markedly inhibited by intra-hypothalamic injection or systemic (i.v.) injections of mazindol. Electro-osmotic mazindol mimicked the effects of glucose in the lateral (inhibition) and ventromedial (excitation) hypothalamus. The results suggest that the inhibitory effects of mazindol on salivary secretion may be through the hypothalamic feeding control centers. Mazindol also directly affected gastric acid secretory neurons in the lateral hypothalamus. It might thus be expected to be effective in the treatment of obesity.
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PMID:[Mazindol effects on the salivary and gastric acid secretory mechanisms]. 674 6

A comparison has been made of the effects of d(+) fenfluramine, Mazindol and Diethylpropion on the changes in body weight and brain ascorbic acid concentrations in male and female guinea pigs receiving vitamin C-deficient diet daily with or without daily supplementary vitamin C for 24 days. Bodyweight increases initially; the subsequent decrease was more rapid in scorbutic male than in the female guinea pigs. The weight-reducing drugs prevented the initial rise in weight of these ascorbutic guinea pigs. Fenfluramine caused the greatest fall in weight in both sexes, the effect being more pronounced in the males. Supplementary vitamin C reduced the anti-obesity actions of fenfluramine, Mazindol and Diethylpropion. Brain ascorbic acid level in scorbutic guinea pigs was more significantly reduced by fenfluramine than by either Mazindol or Diethylpropion after 24 days administration. These drugs prevented the rise in brain ascorbic acid normally produced by supplementary vitamin C. The reduction brain ascorbic acid appears to be related to the loss of weight more in the males than in the females.
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PMID:Vitamin C and weight reducing drugs on brain ascorbic acid in guinea pigs. 732 3

Two patients with Prader-Willi syndrome, including gross obesity with food-related behavior and mild mental retardation, are presented. One patient was an 11-year-old girl with the diagnosis of development delay, hypoactivity, and waxy skin with normal female karyotype. The other patient was a 15-year-old girl with the diagnosis of abnormal chromosome 15. Obesity had been present since early childhood, and it was difficult for them to manage their weight control by means of diet and exercise therapy. With 24-week mazindol administration, they demonstrated marked improvement in weight control during the early period and improvement in pathologic behavior without side effects. Mazindol was given orally, 1.0-2.0 mg/day, in one or two daily doses. Mazindol may prove to be useful in the treatment of patients with Prader-Willi syndrome.
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PMID:Effects of mazindol in two patients with Prader-Willi syndrome. 877 Nov 75

1. The anti-obesity and anti-diabetic effects of mazindol were evaluated in obese diabetic yellow KK mice and C57Bl control mice. 2. The study compound was fed through a gastric tube at a rate of 1 or 2 mg/kg per day (0.01 mol/L HCl as control) for 2 weeks. The following parameters were compared in treated and control animals: bodyweight, food intake, white adipose tissue (WAT) weight, brown adipose tissue (BAT) weight and its thermogenesis, noradrenaline (NA) turnover, blood glucose and serum insulin levels and glucose transporter 4 (GLUT4). 3. Furthermore, bodyweight loss of mice pair-fed the same amount of food as the mazindol-treated mice for 2 weeks was measured. 4. Mazindol significantly decreased food intake and significantly increased guanosine-5'-diphosphate-binding in BAT mitochondria and NA turnover in BAT in both yellow KK and C57Bl groups. The amounts of WAT in subcutaneous, mesenteric and retroperitoneal regions and bodyweights were significantly decreased in both groups. Bodyweight loss in mice pair fed with the mazindol-treated groups was approximately 70% compared with that in the mazindol-treated groups. Furthermore, mazindol decreased the levels of blood glucose and serum insulin during the glucose overloading test in yellow KK mice, but it did not influence the GLUT4 protein concentration in WAT and muscle. 5. These observations suggest that mazindol possesses both an anti-obesity action, due to the inhibition of appetite as well as the activation of BAT thermogenesis via increased NA turnover in BAT, and an anti-diabetic action. Consequently, mazindol may be useful for the treatment of obesity as well as non-insulin-dependent diabetes mellitus in obese persons.
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PMID:Anti-obesity and anti-diabetic effects of mazindol in yellow KK mice: its activating effect on brown adipose tissue thermogenesis. 880 May 69

Catecholamine, dopamine, serotonine (5HT) and neuronal histamine are anorectic monoamines and act as anorectic neurotransmitters. The anorectic agents as modulators of these monoamines inhibit appetite by activating release together with suppressing reuptake of those monoamines. The anorectic agents were classified in clinical use into either alpha 1, beta-adrenergic receptor agonists or 5HT-receptor agonist. Dexfenfluramine, a 5HT-receptor agonist, was inhibited in clinical use because of its cardiac complications including pulmonary hypertension and valvelar disease. Mazindol is an adrenergic agonist and the solitary anti-obesity drug used clinically in Japan. Sibutramine shows the effects of both beta-adrenergic and serotonergic receptor agonists. Sibutramine induces not only appetite suppression but also acceleration of peripheral energy expenditure. No histaminergic anorectics have been employed in the clinical situation to date. L-Histizine, precursor amino acid of endogenous neuronal histamine, is useful for suppression of food intake, lipolytic acceleration of peripheral adipose tissues and enhanced energy expenditure in both animals and humans. L-Histizine thus inspires development of more effective and safer anorectics that can be used without suffering from the rebound phenomenon of body weight.
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PMID:[Monoaminergic anorectic agents]. 1172 32

A simple and convenient high performance liquid chromatographic method with UV detection is described for the determination of mazindol [5-(p-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-ol] and its major metabolite, 2-(2-aminoethyl)-3-(p-chlorophenyl)-3-hydroxyphthalimidine (Met), in human plasma. The analytes were extracted with ethyl acetate from plasma samples and separated on a C18 column using acetonitrile-0.067 mol dm(-3) phosphate buffer (pH 3.5) (24 + 76 v/v) as a mobile phase. The eluates were monitored at 220 nm. Following complete validation and stability studies, the proposed method proved to be sensitive and precise. The limits of detection were 0.07 and 0.08 ng ml(-1) of plasma for mazindol and Met, respectively. The accuracy and recovery were in the ranges 94-102% and 91-102%, respectively, for both compounds. The intra- and inter-assay precisions were less than 7.6 and 9.2%, respectively, for both compounds. The stability of mazindol under different storage conditions, i.e., at room temperature (rt) and 4 degrees C and with freeze-thaw cycles, was also examined. Mazindol was unstable in plasma samples left at rt and 4 degrees C. The method was applied to the determination of mazindol and Met in the plasma of a patient treated for obesity with mazindol.
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PMID:High performance liquid chromatographic determination of mazindol in human plasma. 1176 75

Obesity-related diseases including diabetes, dyslipidemia, and hypertension worsen quality of life of patients and waste medical expenses. To reduce the excess body weight, anti-obesity drugs that reduce appetite or lipid absorption from the intestine have been developed. Only Mazindol can be used in Japan at present, whereas Orlistat was launched and very recently Lorcaserin and Qsymia have been accepted in the US and/or European countries. In addition, a variety of drugs having various mechanisms have been investigated in clinical and basic stages. Some anti-obesity drugs were withdrawn from the market because of their severe adverse effects, however, the tremendous research to develop novel, safety anti-obesity drugs is ongoing.
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PMID:[Current status of medical therapy for obesity and the potential of novel anti-obesity drug development]. 2363 Dec 15


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