ABSTRACT
Sibutramine is one of the very few drugs that are approved for long-term treatment of obesity. Sibutramine is a racemic mixture (RS) containing two equal forms of the R(+) and S(-) enantiomers. In this paper, we have investigated comparative anorexic effect of sibutramine enantiomers and their recemate form in rats. After obtaining two days of baseline results, rats were administered orally either with (RS)-sibutramine or its enantiomers (R)- or (S)-sibutramine at dose levels of 5, 10, 20 mg/kg each for 4 days and body weight, food intake and water intake were measured daily. Locomotor activity score of each rat was also recorded on each day. R-Sibutramine and (RS)-sibutramine produced dose dependant decrease in the body weight and food intake. On the other hand, (S)-sibutramine was shown to increase in these parameters. Neither sibutramine nor it's enantiomers showed any consistent effects on spontaneous motor activity (SMA) scores. In conclusion, (R)-sibutramine is better anorexic than or (RS)-sibutramine or it's (S)-enantiomers.
Subject(s)
Administration, Oral , Animals , Anorexia/chemically induced , Body Weight/drug effects , Cyclobutanes/administration & dosage , Dose-Response Relationship, Drug , Eating/drug effects , Female , Male , Motor Activity/drug effects , Rats , Rats, Wistar , StereoisomerismABSTRACT
The aim of this study is to assess the effects of sibutramine (S) 15 mg/day, fluoxetine (F) 60 mg/day, and metformin (M) 1,700 mg/day, as an adjunct therapy to a 1,500 kcal/day diet, in reducing anthropometric and metabolic parameters. S (n= 8), F (n= 9), and M (n= 8) were compared to placebo (n= 10) in 35 obese patients in a 90-day trial. Side effects were also studied during the treatment. The data demonstrated that F therapy resulted in a greater average reduction in BMI (11.0 percent), weight (10.0 percent), abdominal circumference (11.0 percent) and percentfatty-tissue (12.8). An elevation in HDL-cholesterol (25.8 percent) and a reduction in average triglyceride levels (28.3 percent) were also shown. S presented a 7.91 percent reduction in the abdominal circumference and a 9.65 reduction in percentfatty-tissue was also found. M group presented reductions in BMI (4.03 percent), waist circumference (6.92 percent), HOMA (23.5 percent) and blood pressure (6.08 percent in systolic and 2.08 percent in diastolic). In general, the three drugs can be considered well tolerated. We concluded that F and S demonstrated a greater mean reduction in anthropometric and metabolic parameters when compared to M, however all of them are useful for that purpose, when the subjectsÆ characteristics are considered.
O objetivo deste estudo foi avaliar o efeito da sibutramina (S) 15 mg/dia, fluoxetina (F) 60 mg/dia, e metformina (M) 1.700 mg/dia, associadas a uma dieta de 1.500 kcal/dia, na redução de parâmetros antropométricos e metabólicos. S (n= 8), F (n= 9) e M (n= 8) foram comparadas ao placebo (n= 10) em 35 pacientes obesos durante 90 dias de tratamento. As reações adversas também foram avaliadas durante o tratamento. O grupo F demonstrou uma redução no IMC (11,0 por cento), peso (10,0 por cento), circunferência abdominal (11,0 por cento) e por cento de tecido adiposo (12,8). Também foram observados um aumento nos níveis de HDL-colesterol (25,8 por cento) e uma redução nos níveis de triglicérides (28,3 por cento), no grupo F. O grupo S apresentou uma redução de 7,91 por cento na circunferência abdominal e de 9,65 na por cento de tecido adiposo. Já o grupo M apresentou reduções no IMC (4,03 por cento), circunferência abdominal (6,92 por cento), HOMA (23,5 por cento) e pressão arterial (6,08 por cento na sistólica, 2,08 por cento na diastólica). Os três fármacos analisados foram bem tolerados durante o tratamento. Concluímos que a F e a S demonstraram maior eficácia na redução dos parâmetros antropométricos e metabólicos dos pacientes obesos quando comparadas à M, entretanto todas podem ser prescritas para essa finalidade, desde que sejam consideradas as características individuais dos pacientes.
Subject(s)
Humans , Male , Adolescent , Adult , Middle Aged , Antidepressive Agents, Second-Generation/administration & dosage , Appetite Depressants/administration & dosage , Cholesterol/blood , Hypoglycemic Agents/administration & dosage , Obesity/drug therapy , Analysis of Variance , Antidepressive Agents, Second-Generation/adverse effects , Appetite Depressants/adverse effects , Combined Modality Therapy , Cholesterol/adverse effects , Cyclobutanes/administration & dosage , Cyclobutanes/adverse effects , Fluoxetine/administration & dosage , Fluoxetine/adverse effects , Hypoglycemic Agents/adverse effects , Multicenter Studies as Topic , Metformin/administration & dosage , Metformin/adverse effects , Obesity/diet therapy , Obesity/metabolism , Placebos , Single-Blind MethodABSTRACT
MATERIAL AND METHODS: An open, non-comparative study was carried out to assess the efficacy and toleration profile of sibutramine, a new antiobesity drug, in promoting weight loss in obese type 2 diabetes mellitus subject who failed to reduce weight after strict dietary control. Twenty seven patients completed the study. Sibutramine was started as a single morning dose of 10 mg and was subsequently increased to 15 mg daily if weight loss was not satisfactory. The total duration of the study was twelve weeks with followup at every four weeks. Effect of drug was monitored in terms of weight reduction, changes in body mass index, waist circumference, hip circumference, waist/hip ratio and other metabolic parameters. A fixed dietary prescription and concomitant therapy with drugs, if required and not likely to interfere with the trial therapy, was permitted but was not changed during the study period. RESULTS: At the end of 12 week, mean weight reduction in study subjects was 4.16 kg (p < 0.001), the corresponding BMI decreased by 1.6 (p < 0.0001) and hip circumference by 3.68 (p < 0.001). However, there was no significant change in fasting blood glucose and Hb(A1c) values. CONCLUSION: The study indicates sibutramine to be an effective and well tolerated agent leading to significant reduction in parameter of obesity in obese type 2 diabetic subjects.
Subject(s)
Adult , Aged , Appetite Depressants/administration & dosage , Cyclobutanes/administration & dosage , Diabetes Mellitus, Type 2/complications , Diet, Fat-Restricted , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Male , Middle Aged , Obesity/complications , Prospective Studies , Treatment Failure , Treatment Outcome , Weight Loss/drug effectsABSTRACT
La alopécia areata (AA) es una patología realtivamente frecuente del folículo piloso. Su etiología, si bien es desconocida, probablemente corresponda a un fenómeno autoinmune, aunque factores genéticos y ambientales también estarían involucrados. La inmunoterapia tópica es la modalidad terapéutica más efectiva y aceptada en el tratamiento de la AA crónica severa. La inmunoterapia tópica se define como la inducción y posterior provocación periódica de una dermatitis de contacto alérgica, a través de la aplicación de un potente alergeno de contacto en una zona cutánea determinada. Han sido utilizados tres alergenos de contacto en el tratamiento de la alopecia areata: dinitroclorobenceno (DNCB), dibutil éster del ácido escuárico (SADBE) y difenciprona (DPC). En el presente trabajo se describen las principales características de estos agentes tópicos