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Methylphenidate HCl: therapy for attention deficit hyperactivity disorder

Methylphenidate is a first-line therapy for attention deficit hyperactivity disorder, the most prevalent neuropsychiatric disorder of childhood. The compound is a piperidine and the D-threo-isomer is considered the biologically active form. The compound is available in multiple short- and long-acting preparations, having different delivery systems leading to varying kinetics without clear superiority in efficacy or tolerability at the group level. Common adverse effects are insomnia, appetite disturbance, stomach ache, headache and dizziness. Its mechanism of action is linked to the monoamines dopamine and norepinephrine. The compound appears to predominantly increase the synaptic concentration of dopamine, presumably via inhibition of the dopamine transporter DAT1. There also appears to be effects on presynaptic vesicular trafficking and distribution of dopamine. Both immediate- and sustained-release preparations of methylphenidate have proven efficacy in children and adults with attention deficit hyperactivity disorder. Analysis of the National Institutes of Health-sponsored multimodal treatment study of attention deficit hyperactivity disorder supports a combined medication and behavioral therapy approach.