RESUMO
OBJECTIVE: Obesity is the strongest risk factor for type 2 diabetes (T2D). We aimed to explore 7% weight reduction rates of mazindol alone or combined with metformin in non-diabetic obese Mexican subjects who had additional risk factors for T2D. MATERIALS AND METHODS: In this randomized double-blind study, 137 participants received 1 mg mazindol (n = 65) alone or combined with 500 mg metformin (n = 72), twice a day, for 6 months. RESULTS: Mazindol and mazindol-metformin were similarly effective. However, when subjects were subclassified into non-diabetics and prediabetics, according to glycated hemoglobin (HbA1c) - < 5.7% and 5.7 - 6.4%, respectively - and/or fasting plasma glucose (FPG) - < 100 mg/dL and 100 - 125 mg/dL, respectively -, differences were evident. Prediabetics in the mazindol-metformin group had a higher rate of 7% weight reduction (78.4%, n = 37) compared to prediabetics treated with mazindol (48.3%, n = 29). Furthermore, mazindol-metformin treatment induced significant reductions in fasting plasma insulin, HOMA-IR, and HbA1c in prediabetics compared to mazindol. No differences were found in any parameter between non-diabetics treated with mazindol (n = 36) and mazindol-metformin (n = 35). CONCLUSION: Our results highlight the effectiveness of mazindol-metformin to achieve higher rates of 7% weight reduction and to improve the glycemic profile in prediabetic obese subjects, which could be useful to prevent or delay T2D in these subjects.
Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Estado Pré-Diabético , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Mazindol , Metformina/farmacologia , Metformina/uso terapêutico , Obesidade/complicações , Obesidade/tratamento farmacológico , Estado Pré-Diabético/induzido quimicamente , Estado Pré-Diabético/tratamento farmacológico , Redução de PesoRESUMO
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. Due to the lack of information in primary studies, direct meta-analyses were conducted only for amfepramone and mazindol. Compared to placebo, amfepramone resulted in higher weight loss in the short-term (<180 days; mean difference (MD) -1.281 kg; p<0.05; I2: 0.0%; p=0.379) and long-term (≥180 days; MD -6.518 kg; p<0.05; I2: 0.0%; p=0.719). Only studies with long-term follow up reported efficacy in terms of abdominal circumference and 5-10% weight reduction. These results corroborated the finding that the efficacy of amfepramone is greater than that of placebo. Treatment with mazindol showed greater short-term weight loss than that with placebo (MD -1.721 kg; p<0.05; I2: 0.9%; p=0.388). However, metabolic outcomes were poorly described, preventing a meta-analysis. A mixed treatment comparison corroborated the direct meta-analysis. Considering the high level of risk of bias and the absence of important published outcomes for anti-obesity therapy assessments, this study found that the evaluated drugs showed poor evidence of efficacy in the treatment of overweight and obese patients. Robust safety data were not identified to suggest changes in their regulatory status.
Assuntos
Depressores do Apetite/uso terapêutico , Dietilpropiona/uso terapêutico , Mazindol/uso terapêutico , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Depressores do Apetite/metabolismo , Dietilpropiona/metabolismo , Humanos , Mazindol/metabolismo , Obesidade/metabolismo , Sobrepeso/metabolismo , Viés de Publicação , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , Redução de Peso/efeitos dos fármacosRESUMO
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. In this context, this commentary presents new arguments to contribute to the discussion, as well as recommendations for future studies.
Assuntos
Depressores do Apetite/uso terapêutico , Dietilpropiona/uso terapêutico , Mazindol/uso terapêutico , Obesidade/tratamento farmacológico , Anfetaminas/uso terapêutico , Brasil , Ciclobutanos/uso terapêutico , Aprovação de Drogas , Humanos , Medição de Risco/tendências , Resultado do TratamentoRESUMO
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. Due to the lack of information in primary studies, direct meta-analyses were conducted only for amfepramone and mazindol. Compared to placebo, amfepramone resulted in higher weight loss in the short-term (<180 days; mean difference (MD) -1.281 kg; p<0.05; I2: 0.0%; p=0.379) and long-term (≥180 days; MD -6.518 kg; p<0.05; I2: 0.0%; p=0.719). Only studies with long-term follow up reported efficacy in terms of abdominal circumference and 5-10% weight reduction. These results corroborated the finding that the efficacy of amfepramone is greater than that of placebo. Treatment with mazindol showed greater short-term weight loss than that with placebo (MD -1.721 kg; p<0.05; I2: 0.9%; p=0.388). However, metabolic outcomes were poorly described, preventing a meta-analysis. A mixed treatment comparison corroborated the direct meta-analysis. Considering the high level of risk of bias and the absence of important published outcomes for anti-obesity therapy assessments, this study found that the evaluated drugs showed poor evidence of efficacy in the treatment of overweight and obese patients. Robust safety data were not identified to suggest changes in their regulatory status.
Assuntos
Humanos , Depressores do Apetite/uso terapêutico , Dietilpropiona/uso terapêutico , Mazindol/uso terapêutico , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Depressores do Apetite/metabolismo , Dietilpropiona/metabolismo , Mazindol/metabolismo , Obesidade/metabolismo , Sobrepeso/metabolismo , Viés de Publicação , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , Redução de Peso/efeitos dos fármacosRESUMO
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. Levels of the drug found were higher in plasma when compared with oral fluid and higher in urine in relation to plasma. The study of the mazindol's pharmacokinetics showed that the most suitable model to describe the variation of the concentration over time is the compartment open model with absorption and elimination following the first-order kinetics, and confirming literature data, drug is metabolized, being the major metabolite detected, but not quantified. CONCLUSION: It was not found a good correlation between the concentrations of mazindol in urine and plasma, but between plasma and oral fluid, there was a good correlation, suggesting this as an alternative matrix to plasma. However, studies involving more subjects are needed.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacocinética , Mazindol/farmacocinética , Administração Oral , Adulto , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/urina , Voluntários Saudáveis , Humanos , Masculino , Mazindol/sangue , Mazindol/urina , Modelos Biológicos , Saliva/química , Adulto JovemRESUMO
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. METHOD: The method involved a liquid-liquid extraction of the samples and a LC-MS analysis was fully validated. Method was used to analyze samples of urine and plasma collected from health volunteers in a period of 24h. Metabolite of mazindol was synthesized using alkaline conditions. RESULTS: After validation the method proved to be adequate to analyze samples collected from health volunteers. Method was linear in the concentration range of 0.1-10ng/mL (r=0.9982) for plasma and 5-50ng/mL (r=0.9973) for urine. DISCUSSION: Analysis of the samples showed that mazindol can be detected after 1h of administration and that concentration levels in urine were always higher than in plasma. Mazindol metabolite was detected only in urine.
Assuntos
Cromatografia Líquida/métodos , Mazindol/sangue , Mazindol/urina , Espectrometria de Massas por Ionização por Electrospray/métodos , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/urina , Humanos , Extração Líquido-Líquido/métodos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodosRESUMO
ANTECEDENTES Y CONTEXTO: El mazindol es un estimulante central imidazólico, de efecto similar a las anfetaminas, utilizado fundamentalmente como anorexígeno y también para el tratamiento de otras patologías. Produce excitabilidad, irritabilidad y aumenta el riesgo cardiovascular; también genera rápida tolerancia, dependencia y un alto potencial de abuso. En la actualidad el uso de mazindol es controvertido y ha sido retirado del mercado en la mayoría de los países. OBJETIVO: Evaluar la seguridad y la eficacia del mazindol en la práctica clínica. MÉTODO: Revisión sistemática de la bibliografía obtenida en las bases de datos de estudios publicados desde 1975 a 2016, sin restricción de lenguaje y que evaluaran la eficacia y/o seguridad de mazindol en seres humanos. RESULTADOS: Cumplieron las condiciones de inclusión 20 estudios de un total de 338 encontrados: cuatro revisiones sistemáticas, un metaanálisis, siete ICCAs, tres guías de práctica clínica, dos series de casos, una revisión narrativa, un estudio observacional de corte transversal y un estudio descriptivo. Los estudios incluidos carecen de potencia suficiente para evaluar la eficacia y seguridad del mazindol para los puntos finales evaluados con excepción del tratamiento de la narcolepsia o narcolepsia/cataplexia. En síntesis: -Obesidad Refractaria: Los estudios presentan un limitado número de pacientes y del tiempo de seguimiento. Son de baja calidad metodológica y reportan severos eventos adversos; -Diabéticos con sobrepeso: hay fuerte evidencia para desaconsejar su uso; -Sindrome de Prader Willi: no demostró eficacia; -Distrofia muscular de Aran-Duchenne: no demostró eficacia a los nueve meses de seguimiento; -Narcolepsia y Narcolepsia/Cataplexia: es efectivo, redujo a la mitad o menos la frecuencia de la parálisis del sueño, constituyendo una segunda opción terapéutica luego del modafilino, metilfenidato, oxibato sódica; -Prevención de la recaída en el consumo de cocaína: no hay evidencia de eficacia; -Efectos adversos: los más frecuentes se circunscriben a los sistemas cardiovascular, gastrointestinal y nervioso. Son moderados a severos. El 84% de las notificaciones al Sistema Nacional de Farmacovigilancia están vinculadas a preparaciones magistrales con mazindol. CONCLUSIONES: Las evidencias disponibles, en términos de eficacia, efectividad y riesgo/beneficio, no justifican el uso del mazindol en el tratamiento de la obesidad y de las demás condiciones analizadas a lo largo de esta revisión, excepto para su empleo en el tratamiento de la narcolepsia o narcolepsia/cataplexia como droga de segunda línea cuando los pacientes no responden a modafinilo, metilfenidato u oxibato sódico.(AU)
Assuntos
Humanos , Depressores do Apetite/efeitos adversos , Anfetaminas/efeitos adversos , Mazindol/efeitos adversos , Argentina , Avaliação da Tecnologia Biomédica , Análise Custo-BenefícioRESUMO
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. RESULTS: Acute administration of mazindol decreased complex I activity only in the hippocampus. Complex IV activity was increased in the cerebellum (2.5 mg/kg) and cerebral cortex (0.25 mg/kg). Citrate synthase activity was increased in the cerebellum (1.25 mg/kg) and cerebral cortex (1.25 mg/kg), and creatine kinase activity was increased in the cerebellum (1.25 mg/kg). CONCLUSION: We suggest that the inhibition of complex I in the hippocampus only and activation of complex IV, citrate synthase and creatine kinase occurs because of a stimulus effect of mazindol in the central nervous system, which causes a direct impairment on energy metabolism.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Metabolismo Energético/efeitos dos fármacos , Mazindol/farmacologia , Animais , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/uso terapêutico , Masculino , Mazindol/administração & dosagem , Mazindol/uso terapêutico , Camundongos , Obesidade/tratamento farmacológico , Obesidade/metabolismoRESUMO
Brazil is one of the countries most affected by abuse of stimulant medications by professional drivers, especially fenproporex, amfepramone and mazindol. Even though their sale is banned, they can be found in illegal markets, such as those located on the country's borders. The use of oral fluid to monitor drug levels has many advantages over plasma and urine because it is noninvasive, easier to collect and more difficult to adulterate. The aim of this study was to develop and validate a sensitive and specific method to quantify mazindol in human oral fluid by liquid chromatography-mass spectrometry (LC-MS). The LC system consisted of an LC-MS system operated in selected ion monitoring mode. The mobile phase was composed of water at pH 4.0, acetonitrile and methanol (60:15:25 v/v/v) at a flow rate of 1.0 mL/min and propranolol was used as internal standard. Total running time was 10 min. The lower limit of quantification was 0.2 ng/mL and the method exhibited good linearity within the 0.2-20 ng/mL range (r = 0.9987). A rapid, specific, sensitive, linear, precise and accurate method was developed for determination of mazindol in human oral fluid according to European Medicines Agency guidelines, and is suitable for monitoring mazindol levels in oral fluid of professional drivers.
Assuntos
Estimulantes do Sistema Nervoso Central/análise , Cromatografia Líquida de Alta Pressão/métodos , Mazindol/análise , Saliva/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Condução de Veículo , Brasil , Estimulantes do Sistema Nervoso Central/química , Estabilidade de Medicamentos , Humanos , Modelos Lineares , Masculino , Mazindol/química , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
CONTEXT: No long-term studies have compared centrally acting drugs for treating obesity. OBJECTIVE: To compare the efficacy and safety of diethylpropion (DEP), fenproporex (FEN), mazindol (MZD), fluoxetine (FXT) and sibutramine (SIB) in promoting weight loss. DESIGN AND SETTING: A prospective, randomized, placebo (PCB)-controlled study conducted at a single academic institution. PATIENTS: A total of 174 obese premenopausal women. INTERVENTION: Participants randomly received DEP 75 mg (n=28), FEN 25 mg (n=29), MZD 2 mg (n=29), SIB 15 mg (n=30), FXT 20 mg (n=29) or PCB (n=29) daily over 52 weeks. Diet and physical activity were encouraged. MAIN OUTCOME MEASURES: The primary endpoints were changes in body weight and the proportion of women who achieved at least 5% weight loss by week 52 in the intent-to-treat population. Other measurements included anthropometry, safety, metabolic and cardiovascular parameters. RESULTS: Weight loss was greater than PCB (-3.1±4.3 kg) with DEP (-10.0±6.4 kg; P<0.001), SIB (-9.5±5.9 kg; P<0.001), FEN (-7.8±6.9 kg; P<0.01) and MZD (-7.4±4.9 kg; P<0.01) but not with FXT (-2.5±4.1 kg). Ten (33.3%) women lost⩾5% of their initial weight with PCB, compared with 20 (71.4%; P<0.001) with DEP, 20 (69%; P<0.02) with FEN, 21 (72.4%; P<0.01) with MZD, 22 (73.3%; P<0.001) with SIB and 10 (35.5%) with FXT. Each medically treated group experienced more adverse events compared with PCB (P<0.001). Compared with PCB, constipation was more prevalent with DEP, SIB and MZD (P<0.01); anxiety was more prevalent with DEP (P=0.01); and irritability occurred more frequently with DEP and FEN (P=0.02). Significant improvements in the depression and anxiety scores, binge-eating episodes and quality of life correlated with weight loss. CONCLUSION: The centrally acting drugs DEP, FEN, MZD and SIB were more effective than PCB in promoting weight loss in obese premenopausal women, with a satisfactory benefit-risk profile.
Assuntos
Anfetaminas/uso terapêutico , Fármacos Antiobesidade/uso terapêutico , Ciclobutanos/uso terapêutico , Dietilpropiona/uso terapêutico , Fluoxetina/uso terapêutico , Mazindol/uso terapêutico , Obesidade/tratamento farmacológico , Redução de Peso/efeitos dos fármacos , Adulto , Índice de Massa Corporal , Brasil , Dieta Redutora , Feminino , Seguimentos , Humanos , Obesidade/prevenção & controle , Estudos Prospectivos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVES: The International Narcotics Control Board released its 2005 annual report, highlighting the Brazil population as one of the largest consumers of anorectics. In Brazil, the National Health Surveillance Agency issued the resolution RDC 58/2007 in order to control the prescription and sale of such drugs. In Belém, the biggest city in the Brazilian Amazon region, this resolution came into force in 2008, leading to inspections of drugstores and magistral pharmacies. The aim of this work was to evaluate the consumption of psychotropic anorectic drugs and the impact of RDC 58/2007 on the prescription and dispensing of anorectics in drugstores and magistral pharmacies in Belém. METHODOLOGY: A retrospective quantitative and descriptive study was conducted of records from the Municipal Department of Health Surveillance of Belém, for 2005 to 2008. The differences in findings were regarded significant when p < 0.05. RESULTS: A total of 1,641 balance sheets of drugstores and magistral pharmacies were analyzed. Amfepramone was the most dispensed medication, followed by fenproporex and mazindol. The highest consumption of anorectics occurred in magistral pharmacies. In 2008, there was a significant reduction in dispensing of anorectics, in drugstores as well as in magistral pharmacies. CONCLUSIONS: This study showed that there was a decrease in the dispensing of anorectics after RDC 58/2007 came into force, and that the magistral pharmacies dispensed more of these drugs. This resolution is a remarkable tool in health control, where it is of great benefit to public health and contributes substantially to the rational use of medicines in Brazil.
OBJETIVOS: O International Narcotics Control Board publicou em 2005 sua pesquisa anual que demonstrou que a população brasileira são um dos maiores consumidores de anorexígenos. No Brasil, a Agência Nacional de Vigilância Sanitária publicou a resolução RDC 58/2007 com o objetivo de controlar a prescrição e comercialização deste tipo de medicamento. Em Belém, a maior cidade da Amazônia brasileira, esta resolução entrou em vigor em 2008, levando à inspeções em drogarias e farmácias. Este trabalho propõe avaliar o consumo de psicotrópicos anorexígenos e o impacto da RDC 58/2007 na prescrição e dispensação de anorexígenos nas drogarias e farmácias magistrais de Belém. METODOLOGIA: foi realizado um estudo retrospectivo, quantitativo e descritivo, com dados coletados do Departamento de Vigilância Sanitária de Belém, de 2005 a 2008. Os dados foram considerados quando p < 0,05. RESULTADOS: Um total de 1.641 balanços foram analisados oriundos de drogarias e farmácias magistrais. Anfepramona foi o medicamento mais dispensado, seguido do femproporex e manzidol. O maior consumo de anorexígenos ocorreu nas farmácias magistrais. Em 2008, houve uma redução significativa na dispensação de anorexígenos, tanto em drogarias quanto em farmácias magistrais. CONCLUSÕES: Este estudo demonstrou que houve uma diminuição na dispensação de anorexígenos após a entrada em vigor da RDC 58/2007, e as farmácias magistrais foram responsáveis por um elevado número na dispensação destes medicamentos. Esta resolução é um marco divisor no controle sanitário, para enorme benefício da saúde pública, contribuindo substancialmente para o uso racional de medicamentos no Brasil.
Assuntos
Depressores do Apetite , Vigilância Sanitária , Dietilpropiona , MazindolRESUMO
Prader-Willi Syndrome (PWS) is a multisystemic genetic disease characterized by hypotonia, mental retardation, characteristic facial appearance, hyperphagia, and compulsive eating due to hypothalamic dysfunction. PWS is caused by loss of function of genes located in chromosome 15q11-q13, an area subject to genomic imprinting. Obesity is a major cause of increased morbidity and mortality among patients with PWS. The objective of this study was to analyze the therapeutic options available for the treatment of the obesity in PWS including pharmacological and surgical strategies.
Assuntos
Obesidade/terapia , Síndrome de Prader-Willi/complicações , Adolescente , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Criança , Pré-Escolar , Feminino , Fluoxetina/uso terapêutico , Frutose/análogos & derivados , Frutose/uso terapêutico , Humanos , Lactente , Recém-Nascido , Masculino , Mazindol/uso terapêutico , Obesidade/etiologia , Obesidade/genética , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , TopiramatoRESUMO
A Síndrome de Prader-Willi (SPW) é uma doença complexa, multissistêmica, caracterizada por hipotonia, retardo mental, características dismórficas, hiperfagia e compulsão alimentar devido à disfunção hipotalâmica. SPW ocorre pela perda de função de genes localizados no cromossomo 15q11-13, região que sofre imprinting genômico. Obesidade é a principal causa de morbidade e mortalidade entre pacientes com SPW. O objetivo desta revisão é analisar as opções terapêuticas disponíveis para o tratamento da obesidade na SPW, incluindo a terapia farmacológica e o tratamento cirúrgico.
Prader-Willi Syndrome (PWS) is a multisystemic genetic disease characterized by hypotonia, mental retardation, characteristic facial appearance, hyperphagia, and compulsive eating due to hypothalamic dysfunction. PWS is caused by loss of function of genes located in chromosome 15q11-q13, an area subject to genomic imprinting. Obesity is a major cause of increased morbidity and mortality among patients with PWS. The objective of this study was to analyze the therapeutic options available for the treatment of the obesity in PWS including pharmacological and surgical strategies.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Obesidade/terapia , Síndrome de Prader-Willi/complicações , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Fluoxetina/uso terapêutico , Frutose/análogos & derivados , Frutose/uso terapêutico , Mazindol/uso terapêutico , Obesidade/etiologia , Obesidade/genética , Inibidores Seletivos de Recaptação de Serotonina/uso terapêuticoRESUMO
This review offers an overview of physiological agents, current therapeutics, as well as medications, which have been extensively used and those agents not currently available or non-classically considered anti-obesity drugs. As obesity - particularly that of central distribution - represents an important triggering factor for insulin resistance, its pharmacological treatment is relevant in the context of metabolic syndrome control. The authors present an extensive review on the criteria for anti-obesity management efficacy, on physiological mechanisms that regulate central and/or peripheral energy homeostasis (nutrients, monoamines, and peptides), on beta-phenethylamine pharmacological derivative agents (fenfluramine, dexfenfluramine, phentermine and sibutramine), tricyclic derivatives (mazindol), phenylpropanolamine derivatives (ephedrin, phenylpropanolamine), phenylpropanolamine oxytrifluorphenyl derivative (fluoxetine), a naftilamine derivative (sertraline) and a lipstatine derivative (orlistat). An analysis of all clinical trials - over ten-week long - is also presented for medications used in the management of obesity, as well as data about future medications, such as a the inverse cannabinoid agonist, rimonabant.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Anfetaminas/uso terapêutico , Depressores do Apetite/uso terapêutico , Ensaios Clínicos como Assunto , Ciclobutanos/uso terapêutico , Metabolismo Energético , Homeostase , Humanos , Lactonas/uso terapêutico , Mazindol/uso terapêutico , Orlistate , Piperidinas/uso terapêutico , Pirazóis/uso terapêutico , Rimonabanto , Redução de Peso/efeitos dos fármacosRESUMO
This review offers an overview of physiological agents, current therapeutics, as well as medications, which have been extensively used and those agents not currently available or non-classically considered anti-obesity drugs. As obesity - particularly that of central distribution - represents an important triggering factor for insulin resistance, its pharmacological treatment is relevant in the context of metabolic syndrome control. The authors present an extensive review on the criteria for anti-obesity management efficacy, on physiological mechanisms that regulate central and/or peripheral energy homeostasis (nutrients, monoamines, and peptides), on beta-phenethylamine pharmacological derivative agents (fenfluramine, dexfenfluramine, phentermine and sibutramine), tricyclic derivatives (mazindol), phenylpropanolamine derivatives (ephedrin, phenylpropanolamine), phenylpropanolamine oxytrifluorphenyl derivative (fluoxetine), a naftilamine derivative (sertraline) and a lipstatine derivative (orlistat). An analysis of all clinical trials - over ten-week long - is also presented for medications used in the management of obesity, as well as data about future medications, such as a the inverse cannabinoid agonist, rimonabant.
Esta revisão faz um apanhado dos agentes fisiológicos e terapêutica atual, bem como de medicações que têm sido usadas extensivamente e de outros agentes ainda não disponíveis ou que são consideradas drogas anti-obesidade não clássicas. Como a obesidade - em especial aquela com distribuição central - representa um importante fator desencadeador de resistência à insulina, o seu tratamento farmacológico é relavente no contexto do controle da síndrome metabólica. Os autores apresentam uma revisão extensa dos critérios de eficácia do manuseio anti-obesidade, dos mecanismos fisiológicos que regulam a homeostase energética central e/ou periférica (nutrientes, monoaminas e peptídeos), dos agentes farmacologicamente derivados dos seguintes produtos: beta-fenetilamina (fenfluramina, dexfenfluramina, fentermina e sibutramina), tricíclicos (mazindol), fenilpropanolamina (efedrina, fenilpropanolamina), fenilpropanolamina oxitrifluorofenil (fluoxetina), naftilamina (sertralina) e lipstatina (orlistat). Também é apresentada uma análise de todos os ensaios clínicos com duração maior do que 10 semanas para medicações usadas no manuseio da obesidade, assim como dados sobre medicações futuras, como o agonista canabinóide inverso, rimonabant.
Assuntos
Humanos , Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Obesidade/tratamento farmacológico , Piperidinas/uso terapêutico , Pirazóis/uso terapêutico , Anfetaminas/uso terapêutico , Ensaios Clínicos como Assunto , Ciclobutanos/uso terapêutico , Metabolismo Energético , Homeostase , Lactonas/uso terapêutico , Mazindol/uso terapêutico , Redução de Peso/efeitos dos fármacosRESUMO
The present study examined the interaction between mazindol (MZ), an anorectic drug extensively used in Brazil and opioid/non-opioid endogenous analgesic systems activated by swim-stress. Further, the role of opioid, dopamine and N-methyl-D-aspartate (NMDA) receptors in mediating the analgesic effect was evaluated. The stress-induced analgesia of a 3-min swimming at 32 degrees C (opioid/non-opioid) and 20 degrees C (non-opioid) were assessed using the formalin test. Male Swiss mice were intraperitoneally injected with naloxone (1.0 mg/kg), sulpiride (3.0 mg/kg), MK-801 (0.075 mg/kg) or saline/vehicle 15 min prior, and with MZ (0.5 mg/kg) or saline/vehicle 5 min prior to swimming. The dose of MZ (0.5 mg/kg) did not cause analgesic effect, however, the association of MZ and swim-stress at both temperatures displayed synergistic interaction on analgesia that was blocked by sulpiride and MK-801 but not by naloxone. The present results suggest that MZ and swim-stress acted synergistically on analgesic responses, involving mainly the non-opioid component and possibly mediated by dopamine D2 receptors and NMDA receptors.
Assuntos
Encéfalo/metabolismo , Dopamina/metabolismo , Mazindol/farmacologia , Peptídeos Opioides/metabolismo , Dor/metabolismo , Estresse Fisiológico/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Masculino , Camundongos , Antagonistas de Entorpecentes/farmacologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Dor/tratamento farmacológico , Dor/fisiopatologia , Medição da Dor/efeitos dos fármacos , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/metabolismo , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores Opioides/efeitos dos fármacos , Receptores Opioides/metabolismo , Estresse Fisiológico/fisiopatologiaRESUMO
Objetivo: Marcar el anorexigeno Mazindol, inhibidor del transportador de dopamina(DA), norepinefrina (NE) y serotonina, con Tc99m por método indirecto, con la finalidad de visualizar con SPECT los receptores dopaminergicos localizados en el cuerpo estriado. Material y métodos: se estudiaron con Tc99m-Mazindol, 5 sujetos; 2 voluntarios sanos (1 mujer y 1 hombre, 35-60 años) y 3 pacientes ( 2 mujeres, 1 hombres) entre 35-80 años, 2 con trastornos cognitivos y 1 paciente con enfermedad de Parkinson, referidos para estudio de perfusión cerebral con Tc99m ECD. Mazindol se hizo reaccionar en frió con disulfito de carbono seguido por hidróxido de sodio, agregándose posteriormente ditiocarbamato y luego de 1 hora de incubación a temperatura ambiente, se lo marcó con Tc99m por método indirecto empleando ácido gluconico, calculándose posteriormente el coeficiente de determinación lipofilico del Tc99-Mazindol. Se realizo SPECT cerebral 30-60 minutos después de administrar 925 MBq (25 mCi) de Tc-99m-Mazindol, utilizando una cámara gamma con dos cabezas, opuestas 102 grados. Los parámetros de adquisición fueron: matriz de 128x128,120 imágenes, cada una de 25 seg., orbita circular con movimiento continuo y 258 grados de rotación. En todos los sujetos sé en las imágenes SPECT con Tc99-Mazindol, se visualizó captación cortical y subcortical, las que fueron interpretadas la primera como reflejo de perfusión cerebral y la segunda al cuerpo estriado estructura que reciben inervación DA. La comparación de imágenes en 3 pacientes en quienes se realizó SPECT con Tc99m Mazindol y con Tc99m ECD, muestra , menor intensidad y resolución en la captación cortical con Tc99m-Mazindol que con Tc99m ECD, visualizándose en éstas captación en el cerebelo , no así en las imágenes con Tc99m Mazindol. La diferencia más significativa entre ambos estudios fue visualizar con Tc99m Mazindol captación subcortical, no presentes en el SPECT con Tc99m-ECD...
Assuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Dopamina , Tomografia Computadorizada de Emissão de Fóton Único , Tecnécio , Mazindol , Transporte Biológico Ativo , Transtornos Cognitivos , Receptores DopaminérgicosRESUMO
Antecedentes: Los anorexígenos generalmente no suelen ser de manejo habitual en la práctica clínica psiquiátrica. Sin embargo, es frecuente indicar una amplia gama de psicofármacos a pacientes a los cuales se les ha prescrito medicamentos supresores del apetito por otros profesionales. Esta combinación farmacológica implica una serie de aspectos a considerar en relación a las indicaciones, efectos adversos y fundamentalmente las interacciones propias de los agentes anorexígenos que en algunos casos pueden llegar a provocar complicaciones irreversibles y fatales. Objetivo. Puesta al día de los principales fármacos anorexígenos disponibles en Chile describiendo su clasificación, características, farmacocinética, indicaciones, contraindicaciones, efectos adversos e interacciones. Material y métodos. Revisión actualizada de la literatura especializada. Resultados. Los anorexígenos son coadyuvantes en el tratamiento integral de pacientes obesos. El resultado del tratamiento es mejor si se acompaña de una recuperación de los hábitos alimentarios. Poseen un alto potencial de abuso, dependencia, tolerancia y síndrome de privación. Sus principales efectos son cardiovasculares, gastrointestinales y en el sistema nervioso central. Los más utilizados en Chile entre 1997 y 1998 fueron fetermina, dietilpropión, fenproporex y dexfenfluramina. Discusión. La principal indicación de los anorexígenos es la obesidad. Deben ser prescritos exclusivamente por médicos. Se recomienda su indicación a corto plazo. Poseen importantes interacciones a considerar con IMAOs, ISRSs, descongestionantes, antitusígenos, antialérgicos, anestésicos generales, sustancias ilícitas, alcohol y otras drogas metabolizadas por citocromo P450. Se enfatiza la posibilidad de la producción del síndrome serotoninérgico. Chile, Argentina y Brasil se encuentran entre los principales países consumidores de estimulantes
Assuntos
Humanos , Fármacos Antiobesidade , Depressores do Apetite , Obesidade , Fármacos Antiobesidade , Quimioterapia Adjuvante , Sistema Enzimático do Citocromo P-450 , Dexfenfluramina , Dietilpropiona , Dietilpropiona/efeitos adversos , Dietilpropiona/farmacocinética , Interações Medicamentosas , Fluoxetina , Mazindol , Metanfetamina , Prescrições de Medicamentos , Síndrome da Serotonina/induzido quimicamenteRESUMO
The present work studied the effects of dopaminergic and muscarinic receptor agonists and antagonists on rat locomotor activity and catalepsy. Results showed that carbachol at the highest dose used (10 mg/kg, p.o.) decreased and pimozide at the dose used abolished locomotor activity. Atropine at a low dose (1 mg/kg, p.o.) increased and at a high dose decreased this parameter. Mazindol at a high dose also increased locomotor activity. A significant and dose-dependent increase in the time on the bar was observed in animals treated with carbachol or pimozide as compared to controls. The increase observed with pimozide was greater than 60 s. Effects of carbachol on locomotor activity were observed already after the first drug exposure, but the increased time on bar produced by this drug in the test of catalepsy was observed only after repeated exposure (7th day). The effect of the highest dose (10 mg/kg, p.o.) of atropine (decreased activity) as related to the lowest one was evident at the 7th day, but the increased locomotor activity seen at the low dose was detected already at the first day. There was a predominance of the effect of pimozide on the open field as well as on catalepsy after its association with each one of the three doses of carbachol. The association of atropine and mazindol did not seem to alter locomotor activity and catalepsy as related to each drug alone. Our results indicate that interactions between dopaminergic and cholinergic systems play an important role on behavior and motor functions.