Estudo de segurança da Ritalina® (Cloridrato de Metilfenidato) em animais adultos : aspectos de neurotoxicidade e nefrotoxicidade

• Ano de defesa: 2015
• Autor(a) principal: Salviano, Luiza Herbene Macêdo Soares
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Metilfenidato; Síndromes Neurotóxicas
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/14088

The methylphenidate (MFD) is the most widely used psychostimulant in Brazil for the treatment of Deficit Disorder Attention Deficit Hyperactivity Disorder (ADHD), very frequent neuropsychiatric disorder of childhood, children in school age and adolescence, but is being very prescribed, creating the need to study the safety of its use. The objective was to evaluate the safety of Ritalin in adult animals, covering aspects of neuro- and nephrotoxicity. We evaluated the effects of methylphenidate using neurobehavioural assessment models of anxiety, depression, motor activity and convulsions after acute treatment in adults, it was identified their effects on monoamines levels in the hippocampus and striatum, we investigated the activity of acetylcholinesterase in hippocampus and striatum (cholinergic seizure model), evaluated the effect of MFD in isolated kidney in renal tubular cells on the viability and proliferation of the cell line being studied and evaluated the kidney biochemical parameters in vivo . The MFD increased all parameters analyzed in maze tests at high cross, proving its anxiolytic effect, increased locomotor activity in the open field test, not changing the grooming and rearing, suggesting an anxiolytic effect and desinibitório; In the test route rod, motor skills of the animals was not affected, indicating that the effects of the MFD is not related to the peripheral neuromuscular blockade, but rather caused centrally; The MFD showed antidepressant effect in the forced swimming test, it decreased the immobility time of animals, suggesting further investigation in this context, since the drug is not used in the clinic as an antidepressant. There was an increase in the concentration of biogenic amines studied, corroborating the antidepressant effect observed in the forced swimming model. The test of seizures induced by pilocarpine, the MFD decreased the seizure latency and death, showing a proconvulsivante activity. In addition, decreased AChE activity in the striatum, suggesting a possible mechanism for enhancement of cholinergic seizures in the P400 model. The MFD reduced urine flow, glomerular filtration and tubular transport of sodium percentage (Tna +%) compared with the control group. In in vivo experiments, with 24 and 48 hours after treatment with MFD, the parameters of renal function: urea, creatinine, creatinine clearance, excretion of Na + and K + have not changed. The MFD did not cause histological changes in kidneys after 24 and 48 h of treatment. In tests with renal tubular cells MDCK, the MFD did not reduce the viability of renal epithelial cells of the distal tubule. From the results, although the MFD appears to be a safe choice for the treatment of ADHD, it should be used with caution, since changes were detected in the parameters of renal function, suggesting a possible nephrotoxic effect and should be investigated in more depth, to evaluate the intensity of these long-term effects.