Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder
1Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. twilens@partners.org
Abstract:
Stimulants are part of the standard-of-care treatment for attention-deficit/hyperactivity disorder (ADHD). Methylphenidate, with a history of use spanning approximately 5 decades, is a first-line stimulant treatment for ADHD. Methylphenidate chiefly affects the prefrontal cortex and striatum, the mechanism of action being modulation of catecholaminergic tone. Methylphenidate treatment produces an increase in dopamine (DA) signaling through multiple actions, including blockade of the DA reuptake transporter and amplification of DA response duration, disinhibition of DA D2 autoreceptors and amplification of DA tone, and activation of D1 receptors on the postsynaptic neuron. The actions of methylphenidate may also be mediated by stimulation of the noradrenergic alpha2 receptor and DA D1 receptor in the cortex. The role of other neurotransmitters such as histamine, acetylcholine, serotonin, and alpha-agonists in modulating catecholamine pathophysiology in ADHD and ADHD treatment needs to be elucidated. Overall, the changes in catecholaminergic tone clinically manifest as improvements in attention deficit, distractibility, and motor hyperactivity in patients with ADHD.
More Related Videos
Related Concept Videos
Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings.
Adrenergic Agonists: Mixed-Action Agents
Ephedrine and pseudoephedrine lack a catecholamine group, making them less susceptible to degradation by metabolic enzymes. They have increased oral bioavailability and lipophilicity, resulting in a longer duration of action. Their response is reduced by...
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
CNS Stimulants: Cocaine, Amphetamines and Cannabinoids
Drugs Affecting Neurotransmitter Synthesis
Drugs Affecting Neurotransmitter Release or Uptake


