Neurobiology of Attention-Deficit/Hyperactivity Disorder and the Action Mechanism of OROS Methylphenidate

ABSTRACT

This article is to review neurobiology of attention-deficit/hyperactivity disorder (ADHD) and pharmacological properties of Osmotic-Controlled Release Oral delivery System Methylphenidate (OROS MPH)(Concerta Oros(R)) in celebration of its one-decade clinical experiences in Korea. ADHD is a highly heritable neurodevelopmental disorder, characterized by age-inappropriate inattention, hyperactivity and impulsiveness. The symptoms of ADHD are consistent with dysfunction of the prefrontal cortex (PFC). The PFC functions such as working memory and executive function are powerfully modulated by the catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE). Methylphenidate (MPH) is a first line treatment for children and adolescents with ADHD in Korea. MPH improves the PFC functions with the mechanism of action being modulation of DA and NE tones by blocking both dopamine transporter (DAT) and norepinephrine transporter (NET). Stimulation of D1 and NE alpha2 receptors on the postsynaptic neurons may be its main mechanisms of action which improve working memory and behavioral inhibition in patients with ADHD. OROS MPH, one of long-acting MPH, employs an osmotic-releasing oral system (OROS), which has been designed to have 12 hour duration of effect, which permits oncedaily dosing, which has been shown to be as effective as 3-times-a-day immediate-release formulation of MPH (IR MPH). Recently there is growing evidence that OROS MPH has positive effects even on adults with ADHD, in multidimensional aspects; cognitively, emotionally and functionally.