The activity mechanisms in ADHD of the various drugs used have not been clearly established. 

Methylphenidate is a CNS stimulant. Its activity is thought to stem from blocking the reuptake of dopamine and noradrenaline into the presynaptic neurone in the corpus striatum, the motor and reward centre in the brain. This increases the availability of these monoamines in the fluid outside the neurones without triggering further dopamine release.¹⁴

Lisdexamfetamine is a prodrug for dexamfetamine which is a centrally acting sympathomimetic amine. The mode of action in ADHD is thought to be similar to methylphenidate. Dexamfetamine may be better tolerated in patients whose symptoms are responding to lisdexamfetamine but cannot tolerate the longer effect profile. While dexamfetamine may be addictive, lisdexamfetamine is not considered so.^1,14,15,16

Atomoxetine, a centrally acting sympathomimetic, is a highly selective and potent inhibitor of the pre-synaptic noradrenaline transporter. It does not directly affect serotonin or dopamine transporters, or other noradrenaline receptor types. It is not a psychostimulant and is not an amphetamine derivative.¹⁴

Guanfacine is a selective alpha-2A adrenergic receptor agonist with no stimulant activity. ADHD activity may derive from direct modification of synaptic noradrenalin transmission at the alpha2A-adrenergic receptors which modulates signalling in the prefrontal cortex and basal ganglia.¹⁴