Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats

The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS) and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days). After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip) and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

Evaluation of Na+, K+-ATPase activity in the brain of young rats after acute administration of fenproporex

Objectives: Fenproporex is an amphetamine-based anorectic which is rapidly converted into amphetamine in vivo. Na+, K+-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that the effects of fenproporex on brain metabolism are poorly known and that Na+, K+-ATPase is essential for normal brain function, this study sought to evaluate the effect of this drug on Na+, K+-ATPase activity in the hippocampus, hypothalamus, prefrontal cortex, and striatum of young rats. Methods: Young male Wistar rats received a single injection of fenproporex (6.25, 12.5, or 25 mg/kg intraperitoneally) or polysorbate 80 (control group). Two hours after the last injection, the rats were killed by decapitation and the brain was removed for evaluation of Na+, K+-ATPase activity. Results: Fenproporex decreased Na+, K+-ATPase activity in the striatum of young rats at doses of 6.25, 12.5, and 25 mg/kg and increased enzyme activity in the hypothalamus at the same doses. Na+, K+-ATPase activity was not affected in the hippocampus or prefrontal cortex. Conclusion: Fenproporex administration decreased Na+, K+-ATPase activity in the striatum even in low doses. However, in the hypothalamus, Na+, K+-ATPase activity was increased. Changes in this enzyme might be the result of the effects of fenproporex on neuronal excitability. .

Impact of health legislation on the sale of anorectics in a city in the Amazon region / Impacto da legislação sanitária na comercialização de anorexígenos em uma cidade da Amazônia

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.

Avaliação toxicológica e reprodutiva de camundongos machos adultos tratados com femproporex / Fenproporex treatment in male mice: behavior and toxicology reproductive analysis

O femproporex é utilizado no mundo todo como potente anorexígeno. Este estudo visa esclarecer se o uso diário de femproporex provoca toxicidade comportamental e/ou reprodutiva em camundongos machos adultos. Para tanto, foram utilizados 40 camundongos, divididos em quatro grupos experimentais, cada um contendo dez animais. Um dos grupos recebeu, via gavage, apenas água, e os outros foram tratados diariamente com femproporex, nas doses de 7,5, 15 e 30 mg kg-1, por um período de 40 dias. Como resultados, verificou-se que o femproporex não alterou a evolução normal da massa dos animais analisados, e concluiu-se que a utilização da droga não promoveu toxicidade comportamental, verificada nos testes de natação forçada e de campo aberto; e reprodutiva, quando verificados genotoxicidade, síntese de testosterona, morfologia de espermatozóides e histologia testicular. Assim sendo, concluiu-se que o femproporex, na concentração e delineamentos experimentais propostos por este trabalho, não apresentou potencial toxicológico

Fenproporex is used worldwide as a powerful anorectic drug. This study was designed to evaluate whether daily intake of fenproporex would lead to behavioral and/or reproductive toxicity in adult male mice. Fourty male mice were used, divided into 4 groups of 10 animals each. The control group received only water by gavage, whereas the experimental groups were treated daily with fenproporex in the doses of 7.5, 15 and 30 mg kg-1, for a period of 40 days. The results demonstrated that fenproporex did not alter the normal evolution of the animals' body mass; it also showed that the use of the drug did not promote behavioral toxicity (open- and forced-swimming tests) or reproductive toxicity (genotoxicity, changes in the morphology of spermatozoa and testicular histology). Thus, the present results indicate that fenproporex, in the evaluated dose and experimental conditions, does not present behavioral and reproductive toxic potential in mice.