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Article Dans Une Revue Trends in Pharmacological Sciences Année : 2017

Contribution of Clinical Neuroimaging to the Understanding of the Pharmacology of Methylphenidate

Résumé

Methylphenidate (MPH) is currently the most widely used molecule in the pharmacologic treatment of attention-deficit hyperactivity disorder (ADHD). Although experience of its application now extends over several decades, its psychotropic nature, prolonged use in children, and chemical relation to amphetamines still raise doubts in the minds of prescribers and the families of the patients. Brain imaging has shed considerable light on the neuropharmacology of MPH. The two main in vivo neuroimaging techniques are positron-emission tomography (PET) and magnetic resonance imaging (MRI), and these can be applied in both animal models and humans. The present review seeks to show how human molecular and functional imaging has contributed to determining not only the molecular targets of MPH, and the action kinetics of the various pharmaceutical forms available, but also the connectivity and brain networks activated by treatment. We also discuss the perspectives opened up by new hybrid PET–MRI techniques that enable multimodal tracking of the impact of methylphenidate on neurotransmission. Trends One of the main pharmacologic treatments for ADHD is MPH. Although MPH is a psychostimulant studied in many clinical trials, many issues have remained unresolved regarding pharmacologic mechanisms, brain bioavailability, pharmacokinetic/pharmacodynamic relations, impacts on brain neurochemistry and connectivity, and positive and negative long-term effects. The development of anatomic, isotopic, molecular, and functional brain imaging has made a considerable contribution to our knowledge of MPH. In humans, PET imaging explores MPH brain bioavailability and molecular targeting of dopamine and norepinephrine transporters; MRI explores the neuroanatomic and functional effects of MPH. New hybrid PET–MRI cameras enable multimodal exploration protocols generating simultaneous pharmacokinetic/pharmacodynamic modeling data for MPH.
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Dates et versions

hal-01689783 , version 1 (22-01-2018)

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Luc Zimmer. Contribution of Clinical Neuroimaging to the Understanding of the Pharmacology of Methylphenidate. Trends in Pharmacological Sciences, 2017, 38 (7), pp.608 - 620. ⟨10.1016/j.tips.2017.04.001⟩. ⟨hal-01689783⟩
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