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The Cochrane Database of Systematic... Jan 2005Obesity is closely related to type 2 diabetes and long-term weight reduction is an important part of the care delivered to obese persons with diabetes. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obesity is closely related to type 2 diabetes and long-term weight reduction is an important part of the care delivered to obese persons with diabetes.
OBJECTIVES
To assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes.
SEARCH STRATEGY
Computerized searches were performed of MEDLINE (January 1966 to May 2004), EMBASE (January 1974 to May 2004, Web of Science (January 1981 to May 2004, and other electronic bibliographic databases, supplemented with hand searches of reference lists and selected journals.
SELECTION CRITERIA
Randomized, controlled trials were included where pharmacotherapy was used as the primary strategy for weight loss among adults with type 2 diabetes. Published and unpublished literature in any language and with any study design was included.
DATA COLLECTION AND ANALYSIS
Two reviewers abstracted data and the quality of included studies was evaluated by assessing potential attrition, as well as selection and measurement bias, and a Jadad score was obtained. Effects were combined using a random effects model.
MAIN RESULTS
A sufficient number of studies were available for a quantitative synthesis for fluoxetine, orlistat, and sibutramine. Twenty two randomized controlled trials were included in the review, with a total of 296 participants for fluoxitine, 2036 for orlistat, and 1047 for sibutramine. Pharmacotherapy produced modest reductions in weight for fluoxetine (5.1 kg (95% confidence interval [CI], 3.3 - 6.9) at 24 to 26 weeks follow up; orlistat 2.0 kg (CI, 1.3 - 2.8) at 12 to 57 weeks follow-up, and sibutramine 5.1 kg (CI, 3.2 - 7.0) at 12 to 52 weeks follow-up. Glycated hemoglobin also modestly and significantly reduced for fluoxetine and orlistat. Gastrointestinal side effects were common with orlistat; tremor, somnolence and sweating with fluoxetine; and palpitations with sibutramine. Some studies, using a variety of study designs, were available on other drugs and a significant decrease in weight was noted in three studies of mazindol, one of phenmetrazine, two of phentermine. No studies were identified that fit inclusion criteria for pseudophedrine, ephedra, sertraline, yohimbine, amphetamine or its derivatives, bupropion, topiramate, benzocaine, threachlorocitric acid, sertraline, and bromocriptine.
AUTHORS' CONCLUSIONS
Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes.
Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Diabetes Mellitus, Type 2; Fluoxetine; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Weight Loss
PubMed: 15674929
DOI: 10.1002/14651858.CD004096.pub2 -
Frontiers in Pharmacology 2015Understanding of drug binding to the human biogenic amine transporters (BATs) is essential to explain the mechanism of action of these pharmaceuticals but more... (Review)
Review
Understanding of drug binding to the human biogenic amine transporters (BATs) is essential to explain the mechanism of action of these pharmaceuticals but more importantly to be able to develop new and improved compounds to be used in the treatment of depression or drug addiction. Until recently no high resolution structure was available of the BATs and homology modeling was a necessity. Various studies have revealed experimentally validated binding modes of numerous ligands to the BATs using homology modeling. Here we examine and discuss the similarities between the binding models of substrates, antidepressants, psychostimulants, and mazindol in homology models of the human BATs and the recently published crystal structures of the Drosophila dopamine transporter and the engineered protein, LeuBAT. The comparison reveals that careful computational modeling combined with experimental data can be utilized to predict binding of molecules to proteins that agree very well with crystal structures.
PubMed: 26441663
DOI: 10.3389/fphar.2015.00208 -
The Medical Journal of Malaysia Jun 1993
Topics: Female; Humans; Infant, Newborn; Mazindol; Obesity; Pregnancy; Pregnancy Complications; Teratogens
PubMed: 8350808
DOI: No ID Found -
British Medical Journal (Clinical... Apr 1985Twenty patients with the narcoleptic syndrome were treated separately with dexamphetamine sulphate tablets 10 and 30 mg, Dexedrine Spansules 10 mg, mazindol 4 mg, and... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Twenty patients with the narcoleptic syndrome were treated separately with dexamphetamine sulphate tablets 10 and 30 mg, Dexedrine Spansules 10 mg, mazindol 4 mg, and fencamfamin hydrochloride 60 mg daily. Each drug was given for four weeks and the effects compared. In these dosages the reported frequency of attacks of narcolepsy was roughly halved with each treatment, dexamphetamine 30 mg daily being only slightly more potent than 10 mg. The subjective effects of Dexedrine tablets and Spansules could not be distinguished by most patients. Effects on mood, alertness, and sympathomimetic side effects were largely inseparable with all these drugs, but a decrease in appetite was not reported by patients with narcolepsy.
Topics: Adult; Aged; Amphetamines; Central Nervous System Stimulants; Female; Humans; Indoles; Male; Mazindol; Middle Aged; Narcolepsy; Norbornanes
PubMed: 2859077
DOI: 10.1136/bmj.290.6476.1167 -
Journal of Pharmacological Sciences 2011The merits and demerits of food with health claims for the prevention of metabolic syndrome (MS) are reviewed. One major underlying cause of MS is obesity. Diet and... (Review)
Review
The merits and demerits of food with health claims for the prevention of metabolic syndrome (MS) are reviewed. One major underlying cause of MS is obesity. Diet and lifestyle changes remain the cornerstones of therapy for obesity, but resulting weight loss is often small and long-term success is extremely uncommon and disappointing. Many anti-obesity drugs have been associated with unintended therapeutic outcomes. Currently, only one drug (mazindol) is approved in Japan for short-term treatment of individuals with a BMI over 35 kg/m(2). Treatment with orlistat with dietary modification, caffeine, or protein supplementation; consuming a low-fat diet; adherence to physical activity routines; prolonged contact with participants; problem-solving therapy; and the alternative treatment of acupressure are efficacious in reducing weight regain after weight loss treatment. Because obesity is highly stigmatized, any effective treatment should be made available to improve quality of life and self-image. Therefore, it is necessary to provide information to consumers through the media concerning 1) basic knowledge about health foods and laws concerning them, 2) scientifically based information on safety/effectiveness of health foods and food elements, and 3) reports on health disturbances associated with health foods around the world.
Topics: Anti-Obesity Agents; Consumer Health Information; Food, Organic; Humans; Japan; Mazindol; Metabolic Syndrome; Models, Biological; Obesity
PubMed: 21436603
DOI: 10.1254/jphs.10r36fm -
Drug Design, Development and Therapy 2014Mazindol has been proposed as a potential treatment of children with attention deficit/hyperactivity disorder (ADHD). The purpose of this pilot study was to assess its...
OBJECTIVE
Mazindol has been proposed as a potential treatment of children with attention deficit/hyperactivity disorder (ADHD). The purpose of this pilot study was to assess its pharmacokinetics, short-term efficacy, and safety.
SUBJECTS AND METHODS
A total of 24 children (aged 9-12 years) with ADHD (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text-revision criteria) received a daily dose of 1 mg for 7 days and were followed for 3 additional weeks. Pharmacokinetic samples were collected after the first administration. ADHD symptoms were assessed using the ADHD Rating Scale (RS)-IV, Conners' Parent Rating Scale - Revised: Long (CPRS-R:L) at screening, baseline, and the end of the study. The Clinical Global Impression - Severity (CGI-S) scale was assessed at baseline, and the CGI - Improvement (CGI-I) scale was assessed at subsequent visits.
RESULTS
Twenty-one subjects (aged 10±1 years) were analyzed. Pharmacokinetic data were described by a one-compartment model with first-order absorption, elimination, and lag time. The typical apparent clearance and apparent volume of distribution were 27.9 L/h and 234 L, and increased with fat-free mass and age, respectively. The mean change in score in ADHD RS-IV after 1 week of mazindol was -24.1 (P<0.0001), greater than a 90% improvement from baseline. Reduction of CPRS-R:L and CGI-S scores were -52.1 (P<0.0001) and -2.5 (P<0.01), respectively. Adverse events were mild to moderate, decreased appetite and upper abdominal pain being the most common.
CONCLUSION
This preliminary study shows that mazindol might be an effective, well-tolerated, and long-acting (more than 8 hours) agent for the treatment of ADHD in children.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Drug Administration Schedule; Female; Humans; Male; Mazindol; Pilot Projects; Safety
PubMed: 25525331
DOI: 10.2147/DDDT.S65495 -
Journal of Neurochemistry Sep 1997The present study addresses the possibility that there are different cocaine-related and mazindol-related binding domains on the dopamine transporter (DAT) that show...
The present study addresses the possibility that there are different cocaine-related and mazindol-related binding domains on the dopamine transporter (DAT) that show differential sensitivity to cations. The effects of Zn2+, Mg2+, Hg2+, Li+, K+, and Na+ were assessed on the binding of [3H]mazindol and [3H]WIN 35,428 to the human (h) DAT expressed in C6 glioma cells under identical conditions for intact cell and membrane assays. The latter were performed at both 0 and 21 degrees C. Zn2+ (30-100 microM) stimulated binding of both radioligands to membranes, with a relatively smaller effect for [3H]mazindol; Mg2+ (0.1-100 microM) had no effect; Hg2+ at approximately 3 microM stimulated binding to membranes, with a relatively smaller effect for [3H]mazindol than [3H]WIN 35,428 at 0 degrees C, and at 30-100 microM inhibited both intact cell and membrane binding; Li+ and K+ substitution (30-100 mM) inhibited binding to membranes more severely than to intact cells; and Na+ substitution was strongly stimulatory. With only a few exceptions, the patterns of ion effects were remarkably similar for both radioligands at both 0 and 21 degrees C, suggesting the involvement of common binding domains on the hDAT impacted similarly by cations. Therefore, if there are different binding domains for WIN 35,428 and mazindol, these are not affected differentially by the cations studied in the present experiments, except for the stimulatory effect of Zn2+ at 0 and 21 degrees C and Hg2+ at 0 degrees C.
Topics: Animals; Carrier Proteins; Cations, Divalent; Cations, Monovalent; Cell Membrane; Cocaine; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors; Glioma; Humans; Kinetics; Lithium; Magnesium; Mazindol; Membrane Glycoproteins; Membrane Transport Proteins; Mercury; Nerve Tissue Proteins; Potassium; Protein Binding; Rats; Sodium; Tritium; Tumor Cells, Cultured; Zinc
PubMed: 9282933
DOI: 10.1046/j.1471-4159.1997.69031106.x -
Naunyn-Schmiedeberg's Archives of... Jul 2004The norepinephrine transporter (NET) is the carrier that drives the neuronal norepinephrine uptake mechanism (uptake1) in mammalian hearts. The radioligand [3H]mazindol... (Comparative Study)
Comparative Study
The norepinephrine transporter (NET) is the carrier that drives the neuronal norepinephrine uptake mechanism (uptake1) in mammalian hearts. The radioligand [3H]mazindol binds with high affinity to NET. In this study, the kinetics of [3H]mazindol binding to NET were measured using a rat heart membrane preparation. Results from these studies were used to set up saturation binding assays designed to measure cardiac NET densities (Bmax) and competitive inhibition assays designed to measure inhibitor binding affinities (KI) for NET. Saturation binding assays measured NET densities in rat, rabbit, and canine hearts. Assay reproducibility was assessed and the effect of NaCl concentration on [3H]mazindol binding to NET was studied using membranes from rat and canine hearts. Specificity of [3H]mazindol binding to NET was determined in experiments in which the neurotoxin 6-hydroxydopamine (6-OHDA) was used to selectively destroy cardiac sympathetic nerve terminals in rats. Competitive inhibition studies measured KI values for several NET inhibitors and substrates. In kinetic studies using rat heart membranes, [3H]mazindol exhibited a dissociation rate constant koff=0.0123+/-0.0007 min(-1) and an association rate constant kon=0.0249+/-0.0019 nM(-1)min(-1). In saturation binding assays, [3H]mazindol binding was monophasic and saturable in all cases. Increasing the concentration of NaCl in the assay buffer increased binding affinity significantly, while only modestly increasing Bmax. Injections of 6-OHDA in rats decreased measured cardiac NET Bmax values in a dose-dependent manner, verifying that [3H]mazindol binds specifically to NET from sympathetic nerve terminals. Competitive inhibition studies provided NET inhibitor and substrate KI values consistent with previously reported values. These studies demonstrate the high selectivity of [3H]mazindol binding for the norepinephrine transporter in membrane preparations from mammalian hearts.
Topics: Animals; Binding, Competitive; Dogs; Dose-Response Relationship, Drug; Heart Rate; Hydroxydopamines; Kinetics; Mazindol; Methods; Myocardium; Norepinephrine Plasma Membrane Transport Proteins; Rabbits; Radioligand Assay; Rats; Rats, Sprague-Dawley; Sodium Chloride; Species Specificity; Symporters; Tritium
PubMed: 15300361
DOI: 10.1007/s00210-004-0949-y -
British Medical Journal Mar 1980
Topics: Body Weight; Dehydration; Drug Synergism; Female; Humans; Indoles; Lithium; Mazindol; Middle Aged
PubMed: 7363020
DOI: 10.1136/bmj.280.6215.684-a -
Endocrine Journal Dec 1996The present investigations were performed in order to clarify the effects of mazindol on body weight and insulin sensitivity in patients with morbid obesity who had...
The present investigations were performed in order to clarify the effects of mazindol on body weight and insulin sensitivity in patients with morbid obesity who had already been treated with a very-low-calorie diet containing 480 kcal food (VLCD) with various amino acids. We attempted to study whether a further decrease in body weight would be achieved by the administration of mazindol, because it is difficult to obtain sufficient and continuous reduction of body weight after VLCD therapy. Thirteen female severely obese subjects were 51.0 +/- 13.9 years old (25-73 years old), with a mean height of 154.7 +/- 5.6 cm (146.0-160.5 cm), mean weight of 84.5 +/- 9.4 kg (69-98 kg) and a mean body mass index (BMI) of 35.3 +/- 3.6 kg/m2 (29.2-41.0 kg/m2). Their mean body weight decreased to 76.7 +/- 2.2 kg (net decrease: 6.3 +/- 0.9 kg) after VLCD therapy for 2-4 weeks. Then they were treated by the administration of mazindol with diet restriction (1000-1200 kal/day). Mazindol administration resulted in a further weight reduction of 2.9 +/- 0.5 kg after 4 weeks, 4.9 +/- 0.5 kg after 8 weeks and 6.9 +/- 0.9 kg after 12 weeks. Their blood pressure was not changed after mazindol treatment. The responses of blood glucose and insulin levels in a 75 g oral glucose tolerance test (OGTT) were not significantly different before and after mazindol administration. The blood glucose area calculated from the data obtained during OGTT for 120 min did not significantly differ before and after mazindol administration, while the insulin area significantly decreased after mazindol treatment (from 98.0 +/- 12.1 before administration to 70.1 +/- 7.8). The mean M value reflecting insulin sensitivity in the whole body determined by euglycemic glucose clamping was increased significantly after mazindol treatment (from 4.92 +/- 0.30 mg/kg/min to 6.36 +/- 0.43 mg/kg/min). The results demonstrated that mazindol administration with diet restriction further reduced body weight in the morbidly obese subjects after treatment with VLCD, with an increase in the M value and a decrease in insulin release. The results suggest that mazindol is useful for reducing body weight as well as improving insulin sensitivity.
Topics: Adult; Aged; Appetite Depressants; Blood Glucose; Body Mass Index; Body Weight; Diet, Reducing; Energy Intake; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Mazindol; Middle Aged; Obesity, Morbid
PubMed: 9075607
DOI: 10.1507/endocrj.43.671