Pharmacological Treatment of ADHD

Mechanism Of Action

ADHD is associated with lower levels of Dopamine and Norepinephrine (DA and NA) in prefrontal cortex (PFC) and both of these stimulants act by increasing concentration of DA and NA in the synaptic cleft; MPH acts on the reuptake channels allosterically, blocks both NA and DA reuptake, thus their levels increase in the synaptic cleft and these then engage dopamine (D1) receptors, improving neurotransmission. Amphetamines, on the other hand are competitive inhibitor and pseudosubstrate for reuptake channels of NE and DA and additionally also facilitates the release of DA via reverse transport.

FMRI study shows that MPH improves the response inhibition, frontal activation and increases striatal activity in ADHD children. The striatal activity is decreased if MPH is given to healthy controls (Vaidya et al, 1998). It also shows improvement in working memory and is related to reduction in rCBF in the dorsolateral prefrontal cortex and posterior parietal cortex.(Mehta et al 2006)