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[This corrects the article doi: 10.6061/clinics/2017(05)10].
March 15, 2018: Clinics
Tim L Wigal, Jeffrey H Newcorn, Nelson Handal, Sharon B Wigal, Ioulietta Mulligan, Virginia Schmith, Eric Konofal
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...
March 19, 2018: CNS Drugs
L E Robledo-González, A Martínez-Martínez, V M Vargas-Muñoz, R I Acosta-González, R Plancarte-Sánchez, M Anaya-Reyes, C Fernández Del Valle-Laisequilla, J G Reyes-García, J M Jiménez-Andrade
BACKGROUND: The role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the anti-nociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund's adjuvant (CFA)-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined. METHODS: Adult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week...
2017: Journal of Pain Research
Rosa Camila Lucchetta, Bruno Salgado Riveros, Roberto Pontarolo, Rosana Bento Radominski, Michel Fleith Otuki, Fernando Fernandez-Llimos, Cassyano Januário Correr
The aim of this study was to evaluate efficacy and safety of amfepramone, fenproporex and mazindol as a monotherapy for the treatment of obese or overweight patients. A systematic review of primary studies was conducted, followed by a direct meta-analysis (random effect) and mixed treatment comparison. Medline and other databases were searched. Heterogeneity was explored through I2 associated with a p-value. Of 739 identified publications, 25 were included in the meta-analysis. The global evaluation of Cochrane resulted in 19 studies with a high level of bias and six with unclear risk...
May 2017: Clinics
Eric Konofal, Cherine Benzouid, Christophe Delclaux, Michel Lecendreux, Elizabeth Hussey
Mazindol is an imidazo-isoindole derivative, a tricyclic compound and a non-amphetamine central nervous system stimulant that blocks dopamine and norepinephrine reuptake. Mazindol was withdrawn from the US and European markets in 1999 for reasons unrelated to its efficacy or safety around a time when other anorexic drugs were found to be associated with the development of pulmonary arterial hypertension (PAH). Despite the use of mazindol for decades, reports of PAH due to mazindol intake have been extremely rare...
June 2017: Sleep Medicine
Rosa Camila Lucchetta, Bruno Salgado Riveros, Roberto Pontarolo, Rosana Bento Radominski, Michel Fleith Otuki, Fernando Fernandez-Llimos, Cassyano Januário Correr
Antiobesity pharmacotherapy remains the main point of disagreement among both scientists and regulators. This is probably due to small sample sizes, high levels of heterogeneity, and low methodological quality. For many years, Brazil was one of the largest consumers of appetite suppressants worldwide, with evidence of irrational use of this drug class. Therefore, the country was the scene of a debate that divided the Brazilian Health Surveillance Agency (Anvisa - Agência Nacional de Vigilância Sanitária) and medical societies over the maintenance record of diethylpropion, mazindol and fenproporex...
March 2017: Revista da Associação Médica Brasileira
Y Kimura, J Maeda, M Yamada, K Takahata, K Yokokawa, Y Ikoma, C Seki, H Ito, M Higuchi, T Suhara
RATIONALE: The beneficial effects of psychostimulant drugs in the treatment of psychiatric disorders occur because they increase the extracellular dopamine concentration by inhibiting re-uptake of extracellular dopamine at dopamine transporters. However, the psychological effects at low dopamine transporter occupancy have not been well demonstrated. OBJECTIVES: The purpose of the study was to evaluate the psychological effects, dopamine transporter occupancy, and dopamine release induced by a single oral administration of a clinical dose of mazindol...
February 2017: Psychopharmacology
Xavier Castells, Ruth Cunill, Clara Pérez-Mañá, Xavier Vidal, Dolors Capellà
BACKGROUND: Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be an effective therapy for treatment. OBJECTIVES: To assess the effects of psychostimulants for cocaine abuse and dependence. Specific outcomes include sustained cocaine abstinence and retention in treatment. We also studied the influence of type of drug and comorbid disorders on psychostimulant efficacy...
September 27, 2016: Cochrane Database of Systematic Reviews
Daisuke Aotani, Cheol Son, Yoshiyuki Shimizu, Hidenari Nomura, Takatoshi Hikida, Toru Kusakabe, Tomohiro Tanaka, Takashi Miyazawa, Kiminori Hosoda, Kazuwa Nakao
In this study, we evaluated the preventive effect of mazindol on the development of obesity and sought to elucidate the drug's effects on the reward system. In mice, body weight gain and hyperphagia induced by high-fat diet (HFD) were decreased by 38.6% and 13.9%, respectively, by subcutaneous infusion of mazindol (1.5mg/kg/day) for 28days. A single intraperitoneal administration of mazindol (1.5mg/kg) significantly reduced lipid preference, as assessed using the two-bottle preference paradigm (vehicle, 89...
October 28, 2016: Neuroscience Letters
Megan L Fitzgerald, Suham A Kassir, Mark D Underwood, Mihran J Bakalian, J John Mann, Victoria Arango
Inconsistent evidence implicates disruptions of striatal dopaminergic indices in suicide and major depression. To determine whether there are alterations in the striatal dopamine system in suicide, we conducted a quantitative autoradiographic survey of dopamine transporter (DAT; [3 H]mazindol), D1 receptor ([3 H]SCH23390), and D2 receptor ([3 H]sulpiride) binding in the dorsal striatum postmortem from matched suicides and controls. Axis I and axis II psychiatric diagnosis, recent treatment history, and early life adversity (ELA) were determined by psychological autopsy...
March 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Marcella Herbstrith de Oliveira, Pâmela Cristina Lukasewicz Ferreira, Graciela Carlos, Fernanda Rodrigues Salazar, Ana Maria Bergold, Flavio Pechansky, Renata Pereira Limberger, Pedro Eduardo Fröehlich
PURPOSE: There are no pharmacokinetics studies in oral fluid reported in the literature, as well as there are no data on correlation of drug levels in plasma, urine, and oral fluid in order to propose alternative matrices to monitor the use of mazindol by drivers. The present work aimed to study, preliminarily, mazindol's pharmacokinetics in plasma and oral fluid, as well as investigate the correlation of drug levels in urine, plasma, and oral fluid. METHOD: Blood, urine, and oral fluid samples from seven healthy male volunteers were collected at 0, 1, 2, 4, 5, 6, 8, 10, and 24 h after administration of tablets of 2 mg mazindol and analyzed by a previously validated method by LC-MS with liquid-liquid extraction...
August 2016: European Journal of Clinical Pharmacology
Cafer Saka
Norepinephrine reuptake inhibitors (NRIs) are a class of antidepressant drugs that act as reuptake inhibitors for the neurotransmitters norepinephrine and epinephrine. The present review provides an account of analytical methods published in recent years for the determination of NRI drugs. NRIs are atomoxetine, reboxetine, viloxazine and maprotiline. NRIs with less activity at other sites are mazindol, bupropion, tapentadol, and teniloxazine. This review focuses on the analytical methods including chromatographic, spectrophotometric, electroanalytical, and electrophoresis techniques for NRI analysis from pharmaceutical formulations and biological samples...
2016: Critical Reviews in Analytical Chemistry
Aaron Janowsky, Dilip K Tosh, Amy J Eshleman, Kenneth A Jacobson
Thirty-two congeneric rigid adenine nucleoside derivatives containing a North (N)-methanocarba ribose substitution and a 2-arylethynyl group either enhanced (up to 760% of control) or inhibited [(125)I] methyl (1R,2S,3S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate (RTI-55) binding at the human dopamine (DA) transporter (DAT) and inhibited DA uptake. Several nucleosides also enhanced [(3)H]mazindol [(±)-5-(4-chlorophenyl)-3,5-dihydro-2H-imidazo[2,1-a]isoindol-5-ol] binding to the DAT. The combination of binding enhancement and functional inhibition suggests possible allosteric interaction with the tropanes...
April 2016: Journal of Pharmacology and Experimental Therapeutics
Marcella Herbstrith de Oliveira, Pâmela Cristina Lukasewicz Ferreira, Graciela Carlos, Fernanda Rodrigues Salazar, Ana Maria Bergold, Flavio Pechansky, Renata Pereira Limberger, Pedro Eduardo Fröehlich
INTRODUCTION: Even after removal of some stimulants, like fenproporex, amfepramone and mazindol, from Brazilian market, the use of these substances is still high, especially by drivers. Mazindol is the second most used anorectic agent in the world acting as an indirect sympathomimetic agonist, having stimulatory action on central nervous system. Plasma is a good matrix to monitor since it reflects the psychomotor effects of these drugs, but unlike urine has an invasive collection; drug levels and detection time are quite low...
May 2016: Journal of Pharmacological and Toxicological Methods
Kazuhiro Nagamine, Hiroaki Ueno, Masamitsu Nakazato
Obesity has been increasing not only in Japan but also in both developed and developing countries. Mean body mass index of Japanese patients with type 2 diabetes has been increasing, and it reached 25.0 in 2013. If body weight decreases more than 3% of initial body weight in patients with metabolic syndrome, not only glucose metabolism but also dyslipidemia and hypertension improve. To reduce the excess body weight, behavior therapy, calorie restriction, and exercise are necessary. The next strategies are drugs including mazindol, glucose-like peptide-1 receptor agonist and sodium-dependent glucose cotransporter 2 inhibitor, and bariatric surgery...
December 2015: Nihon Rinsho. Japanese Journal of Clinical Medicine
O Bonnot, D Cohen, D Thuilleaux, A Consoli, S Cabal, M Tauber
UNLABELLED: Prader-Willi syndrome (PWS) is a rare genetic syndrome. The phenotype includes moderate to intellectual disability, dysmorphia, obesity, and behavioral disturbances (e.g., hetero and self-injurious behaviors, hyperphagia, psychosis). Psychotropic medications are widely prescribed in PWS for symptomatic control. We conducted a systematic review of published literature to examine psychotropic medications used in PWS. MEDLINE was searched to identify articles published between January 1967 and December 2014 using key words related to pharmacological treatments and PWS...
January 2016: European Journal of Pediatrics
Heidi Koldsø, Julie Grouleff, Birgit Schiøtt
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...
2015: Frontiers in Pharmacology
Eric Konofal, Wei Zhao, Cédric Laouénan, Michel Lecendreux, Florentia Kaguelidou, Lila Benadjaoud, France Mentré, Evelyne Jacqz-Aigrain
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...
2014: Drug Design, Development and Therapy
Cinara Ludvig Gonçalves, Giselli Scaini, Gislaine Tezza Rezin, Isabela Casagrande Jeremias, Gisele Daiane Bez, Juliana Felipe Daufenbach, Lara Mezari Gomes, Gabriela Kozuchovski Ferreira, Alexandra Ioppi Zugno, Emilio Luiz Streck
OBJECTIVES: Mazindol is a sympathomimetic amine, widely used as an anorectic agent in the treatment of obesity. This drug causes psychostimulant effects because of its pharmacological profile similar to amphetamine, acting like a monoamine reuptake inhibitor. However, the mechanisms underlying the action of mazindol are still not clearly understood. METHODS: Swiss mice received a single acute administration of mazindol (0.25, 1.25 and 2.5 mg/kg, ip) or saline. After 2 h, the animals were killed by decapitation; the brain was removed and used for the evaluation of activities of mitochondrial respiratory chain complexes, Krebs cycle enzymes and creatine kinase...
June 2014: Acta Neuropsychiatrica
David J Heal, Jane Gosden, Sharon L Smith
The long held view is cocaine's pharmacological effects are mediated by monoamine reuptake inhibition. However, drugs with rapid brain penetration like sibutramine, bupropion, mazindol and tesofensine, which are equal to or more potent than cocaine as dopamine reuptake inhibitors, produce no discernable subjective effects such as drug "highs" or euphoria in drug-experienced human volunteers. Moreover they are dysphoric and aversive when given at high doses. In vivo experiments in animals demonstrate that cocaine's monoaminergic pharmacology is profoundly different from that of other prescribed monoamine reuptake inhibitors, with the exception of methylphenidate...
December 2014: Neuropharmacology
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