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International Journal of Obesity 1977Thirty-eight obese patients, resistant to conventional diet therapy, agreed to consume a 1.09 MJ (260 kcal)/day semi-synthetic diet consisting of 25 g egg albumin, 40 g... (Clinical Trial)
Clinical Trial Comparative Study
Thirty-eight obese patients, resistant to conventional diet therapy, agreed to consume a 1.09 MJ (260 kcal)/day semi-synthetic diet consisting of 25 g egg albumin, 40 g oligosaccharides, vitamins and minerals, and were seen weekly as outpatients for eight weeks. At the beginning, the semi-synthetic diet was given with either the anorectic drug, mazindol (2 mg/day) or a placebo for four weeks and then changed over for the remaining four weeks; the study being conducted on a double-blind basis. The final treatment was a 4.2 MJ (1000 KCAL) conventional diet for a further four weeks without drug or placebo. Twenty-five patients completed the first eight weeks and 21 patients the final four weeks of the trial. The total mean weight losses were as follows: week 4, 9.3 kg; week 8, 13.7 kg; week 12, 12.2 kg. There was no significant difference in weight loss between mazindol treatment and placebo but the former group reported feeling less hungry. The chief side-effects observed were dizziness, nausea, dry mouth, insomnia and depression which were more frequent with mazindol. Six patients had to stop mazindol because of side-effects, but were able to continue the diet alone. It is concluded that a semi-synthetic diet containing 1.09 MJ (260 kcal) daily can be successfully employed in the treatment of obese outpatients, and is a practical therapeutic alternative to admission to hospital. There is no clinical advantage to be gained by the additional use of the anorectic drug, mazindol.
Topics: Adolescent; Adult; Clinical Trials as Topic; Diet, Reducing; Dizziness; Double-Blind Method; Drug Evaluation; Dyspepsia; Female; Food, Formulated; Headache; Humans; Hunger; Indoles; Male; Mazindol; Middle Aged; Nausea; Obesity; Patient Compliance; Placebos
PubMed: 363631
DOI: No ID Found -
CNS Drugs Mar 2018Mazindol is under investigation for the treatment of attention-deficit/hyperactivity disorder (ADHD) because of its alertness-enhancing properties. A novel... (Randomized Controlled Trial)
Randomized Controlled Trial
A Double-Blind, Placebo-Controlled, Phase II Study to Determine the Efficacy, Safety, Tolerability and Pharmacokinetics of a Controlled Release (CR) Formulation of Mazindol in Adults with DSM-5 Attention-Deficit/Hyperactivity Disorder (ADHD).
BACKGROUND
Mazindol is under investigation for the treatment of attention-deficit/hyperactivity disorder (ADHD) because of its alertness-enhancing properties. A novel controlled-release (CR) formulation of mazindol was developed to allow once-daily dosing.
OBJECTIVE
The aim of this study was to evaluate the efficacy of mazindol CR in adults with ADHD.
DESIGN
We conducted a randomized, double-blind, placebo-controlled 6-week trial.
METHODS
Subjects diagnosed with ADHD using the Mini-International Neuropsychiatric Structured Interview (MINI) and with an ADHD Rating Scale, Diagnostic and Statistical Manual of Mental Disorders 5th Edition (ADHD-RS-DSM5) score ≥ 28 were randomized to receive placebo or 1-3 mg/day of mazindol for 6 weeks. The primary endpoint was the reduction from baseline in the ADHD-RS-DSM5 score on Day 42. Secondary endpoints were response rates defined by change in ADHD-RS-DSM5 (≥ 30 or ≥ 50% reduction) and dichotomized Clinical Global Impression-Improvement (CGI-I) score (1 or 2). An exploratory endpoint of functional impairment, as measured by the Target Impairment Scale, examined individualized deficits in specific settings. Safety, tolerability, and pharmacokinetics were assessed.
RESULTS
Eighty-five participants were randomized (n = 43 active, 42 placebo); 75 completed. Weekly ADHD-RS-DSM5 measurements after mazindol differed from placebo beginning at Day 7, with a least squares mean difference (active-placebo) of - 13.2 at Day 42 and an effect size of 1.09. For the 30% or more reduction in ADHD-RS-DSM5 (minimal response), a significant difference (active-placebo) was seen starting at Day 7 and continuing to Day 42. For the CGI-I (1 or 2) and for the 50% or more reduction in ADHD-RS-DSM5 (measures of excellent response), the differences began at Day 14 and continued to Day 42. Functional impairment was significantly different in the proportion achieving at least a 50% reduction in target impairment score (42.9% mazindol vs 11.9% placebo) by Day 42. Dry mouth, nausea, fatigue, heart rate (HR) increased, decreased appetite, and constipation were more prevalent for mazindol versus placebo. Overall, mazindol CR had minimal effects on blood pressure and small effects on HR.
CONCLUSION
Mazindol CR was efficacious in the treatment of adults with ADHD, with a large effect size, and was well tolerated, supporting the progression to phase III. (Clinicaltrials.gov Registration No. NCT02808104).
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Mazindol; Middle Aged; Psychiatric Status Rating Scales; Treatment Outcome; Young Adult
PubMed: 29557078
DOI: 10.1007/s40263-018-0503-y -
Metabolism: Clinical and Experimental Dec 1975Oral administration of a single dose of the anorectic agent mazindol to obese subjects led to a significant improvement in oral glucose tolerance and a concomitant...
Oral administration of a single dose of the anorectic agent mazindol to obese subjects led to a significant improvement in oral glucose tolerance and a concomitant reduction in insulin secretion, but had no effect on the blood glucose and plasma insulin responses to glucose given intravenously. Mazindol, when given to obese subjects in conjunction with a hypocaloric diet, was associated with progressive weight loss and reduction in the fasting levels of blood glucose, plasma insulin, serum triglyceride, and serum cholesterol. When oral glucose tolerance was retested after 16-20 wk, blood glucose and plasma insulin responses were significantly decreased compared with initial control values. It is concluded that one effect of mazindol, when given acutely, is to impair absorption of glucose from the gut. Changes in carbohydrate metabolism after chronic administration of mazindol are entirely consistent with weight loss, although a separate effect of the drug cannot be excluded.
Topics: Glucose; Humans; Indoles; Insulin; Mazindol; Obesity
PubMed: 1196130
DOI: 10.1016/0026-0495(75)90051-7 -
Drug Metabolism and Disposition: the... 1976Three metabolites of tritium-labeled mazindol were isolated from rat urine by the inverse isotope-dilution technique in which the labeled metabolites were synthesized by...
Three metabolites of tritium-labeled mazindol were isolated from rat urine by the inverse isotope-dilution technique in which the labeled metabolites were synthesized by a second, smaller group of rats. These metabolites were isolated by Amberlite XAD-2 chromatography and silica gel column and preparative thin-layer chromatography. The major metabolite (II) was shown by mass spectrometry of its trimethylsilyl derivative. NMR spectroscopy, and degradation studies to be 5-(p-chlorophenyl)-2,5-dihydro-5-hydroxy-3H-imidazol(2,1-a)isoindol-3-one. A comparison of its mass spectrum with that of an authentic sample prepared from 1-(p-chlorophenyl)-3-ethoxy-1-methoxy-1H-isoindole and glycine ethyl ester confirmed the assignment. Metabolite III was shown by its mass spectrum, NMR spectrum, degradation, and analogy with metabolite II to be 5-(p-chlorophenyl)-2,5-dihydro-2,5-dihydroxy-3H-imidazo (2,1-a)isoindol-3-one. Only a small amount of metabolite IV was isolated as an artifact, 3-(p-chlorophenyl)-2-glycyl-3-methoxy-1-isoindolinone, as shown by its mass spectrum and degradation to 2-(p-chlorobenzoy)benzoic acid. The metabolite IV is believed to be the corresponding 3-hydroxy compound. Synthesis of IV by base-catalyzed hydrolysis of metabolite II supports the structural assignment. In addition, the facile conversion of synthetic IV into the corresponding 3-methoxy derivative by acidic methanol was also observed.
Topics: Animals; Chromatography, Thin Layer; Indoles; Magnetic Resonance Spectroscopy; Male; Mazindol; Rats; Spectrophotometry, Infrared
PubMed: 6231
DOI: No ID Found -
The Journal of International Medical... 1977Mazindol is chemically unrelated to the phenethylamines and has not shown the side-effects or abuse potential of the amphetamine anorectics. To further define its... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Mazindol is chemically unrelated to the phenethylamines and has not shown the side-effects or abuse potential of the amphetamine anorectics. To further define its potential for causing weight loss, a six-week double-blind placebo controlled study was undertaken in four centres. A common protocol was used except in one centre, behavioural modification also was employed, whereas in the other centres, no additional measures were used to cause weight loss. Two hundred and forty-five obese patients were assigned randomly to two mazindol groups and one placebo group in each centre. Ninety-eight and forty patients receiving mazindol and placebo respectively completed the protocol. The conclusions were: (a) no significant clinical or laboratory abnormalities occurred from mazindol therapy, (b) the placebo therapy patients did not lose weight without behavioural modification, (c) the placebo therapy group had a higher drop-out rate compared to the mazindol therapy group attributable to the patients' dissatisfaction with failure to lose weight, (d) mazindol therapy without behavioural modification and behavioural modification alone both resulted in a statistically significant mean weight loss of 1 pound/patient/week and (e) mazindol plus behavioural modification resulted in a greater mean weight loss of 1/2 pound/patient/week than with behavioural modification alone. Hence, mazindol is of value in the initial therapy of obesity.
Topics: Adolescent; Adult; Aged; Body Weight; Clinical Trials as Topic; Humans; Indoles; Mazindol; Middle Aged; Obesity; Placebos; Time Factors
PubMed: 326596
DOI: 10.1177/030006057700500202 -
Pediatric Neurology Nov 1995Two 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...
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.
Topics: Adolescent; Appetite Depressants; Central Nervous System Stimulants; Child; Humans; Male; Mazindol; Prader-Willi Syndrome; Weight Loss
PubMed: 8771175
DOI: 10.1016/0887-8994(95)00216-2 -
Neuroscience Letters Jan 1992The effect of mazindol on the dopamine (DA) uptake system in the rat striatum was studied by in vivo voltammetry and microdialysis. An increase in the maximal uptake... (Comparative Study)
Comparative Study
The effect of mazindol on the dopamine (DA) uptake system in the rat striatum was studied by in vivo voltammetry and microdialysis. An increase in the maximal uptake rate was observed by voltammetry 30 min after i.p. administration of 1, 5, 10, 15, and 20 mg/kg doses but not after a dose of 25 mg/kg, while stimulated release was enhanced at all doses. The increased maximal uptake is in contrast to increased levels of extracellular DA observed with microdialysis following mazindol administration. This divergence of action is anomalous in the context of current understanding of the DA uptake system.
Topics: Animals; Corpus Striatum; Dialysis; Dopamine; Dose-Response Relationship, Drug; Electric Stimulation; Electrochemistry; Kinetics; Male; Mazindol; Rats; Rats, Inbred Strains; Reference Values
PubMed: 1589149
DOI: 10.1016/0304-3940(92)90523-a -
Brain Research Bulletin Jul 1985Neuronal responses in the ventromedial hypothalamic nucleus (VMH) to mazindol (MZD) were examined by intracellular recordings in hypothalamic slices in vitro. Bath...
Neuronal responses in the ventromedial hypothalamic nucleus (VMH) to mazindol (MZD) were examined by intracellular recordings in hypothalamic slices in vitro. Bath application of MZD caused depolarization of the membrane by 8.0 +/- 3.4 mV (mean +/- S.D.) associated with an increase in the input membrane resistance (23.0 +/- 5.8%) among 20% of the cells examined. Current-voltage plots, obtained simultaneously, showed the reversal potential between -80 and -90 mV. These results indicate that MZD depolarizes VMH neurons by reducing the K+ conductance, through a mechanism similar to that of glucose, and the anorectic action of MZD can be explained by its direct effects on the VMH.
Topics: Animals; Guinea Pigs; In Vitro Techniques; Indoles; Mazindol; Membrane Potentials; Neurons; Ventromedial Hypothalamic Nucleus
PubMed: 4027704
DOI: 10.1016/0361-9230(85)90057-7 -
International Journal of Psychiatry in...An unusual side effect of amphetamine-like drugs is described. A patient with acute cardiomyopathy was discovered to have been taking Fenfluramine and Mazindol at the...
An unusual side effect of amphetamine-like drugs is described. A patient with acute cardiomyopathy was discovered to have been taking Fenfluramine and Mazindol at the prescribed dose. Within a week after abstention from the drugs and appropriate cardiac treatment her cardiomyopathy resolved. The authors suggest that this effect is due to the combination of the two drugs and represents a drug interaction.
Topics: Adult; Cardiomyopathies; Drug Interactions; Electrocardiography; Female; Fenfluramine; Humans; Indoles; Mazindol
PubMed: 4055256
DOI: 10.2190/yq38-eag3-319r-a8rl -
The Journal of Pharmacology and... Jun 1981Mazindol and two homologs of mazindol were tested for their effects as uptake inhibitors in rat tissue slices for [3H]dopamine in the neostriatum, for [3H]norepinephrine... (Comparative Study)
Comparative Study
Mazindol and two homologs of mazindol were tested for their effects as uptake inhibitors in rat tissue slices for [3H]dopamine in the neostriatum, for [3H]norepinephrine in occipital cortex and for [3H]serotonin in whole brain. All three drugs were potent inhibitors of [3H]dopamine uptake (ED50 values between 57 and 280 nM), [3H]norepinephrine uptake (ED50 values less than 19 nM) and were somewhat weaker against [3H]serotonin uptake (ED50 values between 550 and 4100 nM). All three drugs were in contrast very weak as releasing agents for previously accumulated 3H-biogenic amines. Mazindol injection resulted in a large increase in locomotor activity in mice, but its two homologs were without effect. Mazindol was able to counteract amphetamine-induced increases in activity in reserpinized mice, but its homologs were inactive. Mazindol also caused a vigorous ipsilateral rotation in rats with an unilateral 6-hydroxydopamine lesion of the nigrostriatal system, but again the homologs had no such effect. However, all three drugs were potent inhibitors of prolactin secretion in rats (ID50 values 1-2 mg/kg orally). Correlations between the capacities of the drugs to inhibit 3H-biogenic amine uptake and the various in vivo responses are made.
Topics: Animals; Behavior, Animal; Biogenic Amines; Brain Chemistry; Dopamine; Female; Humans; In Vitro Techniques; Indoles; Male; Mazindol; Mice; Motor Activity; Prolactin; Rats; Solubility; Stereotyped Behavior
PubMed: 7194909
DOI: No ID Found