Mechanism of action

ADHD, and its core symptoms, have been associated with abnormalities in the neural systems that govern release of neurotransmitters such as dopamine and noradrenaline.1-6

Medication-based therapy for ADHD can be described as stimulants, such as methylphenidate,7-14 dexamfetamine15 and lisdexamfetamine dimesylate,16 and non-stimulants, such as atomoxetine17 and guanfacine.18 While the exact mechanism by which these medications reduce ADHD symptoms is not fully known, they are thought to alleviate symptoms of ADHD via similar neurochemical actions in that they enhance synaptic levels of monoamines in the brain, but with different selectivities and molecular mechanisms.19-25

Also named norepinephrine (NE)


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  1. Volkow ND, Wang GJ, Kollins SH, et al. Evaluating dopamine reward pathway in ADHD. JAMA 2009; 302: 1084-1091.
  2. Volkow ND, Wang GJ, Newcorn J, et al. Brain dopamine transporter levels in treatment and drug naïve adults with ADHD. NeuroImage 2007; 34: 1182-1190.
  3. Volkow ND, Wang GJ, Newcorn JH, et al. Motivation deficit in ADHD is associated with dysfunction of the dopamine reward pathway. Mol Psychiatry 2011; 16: 1147-1154.
  4. Volkow ND, Wang GJ, Newcorn JH, et al. Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2007; 64: 932-940.
  5. Costa A, la Fougère C, Pogarell O, et al. Impulsivity is related to striatal dopamine transporter availability in healthy males. Psychiatry Res. 2013; 211: 251-256.
  6. Economidou D, Theobald DE, Robbins TW, et al. Norepinephrine and dopamine modulate impulsivity on the five-choice serial reaction time task through opponent actions in the shell and core sub-regions of the nucleus accumbens. Neuropsychopharmacology 2012; 37: 2057-2006.
  7. Equasym XL Summary of Product Characteristics. Last updated 10 March 2014. Last accessed January 2015.
  8. Ritalin Summary of Product Characteristics. Last updated 15 December 2014. Last accessed January 2015.
  9. Concerta XL 18–36 mg Summary of Product Characteristics. Last updated 14 January 2015. Last accessed January 2015.
  10. Concerta XL 27 mg Summary of Product Characteristics. Last updated 14 January 2015. Last accessed January 2015.
  11. Medikinet Summary of Product Characteristics. Last updated 21 December 2011. Last accessed January 2015.
  12. Medikinet XL 5 mg Summary of Product Characteristics. Last updated 21 December 2011. Last accessed January 2015.
  13. Medikinet XL 10–40 mg Summary of Product Characteristics. Last updated 08 November 2013. Last accessed January 2015.
  14. Medikinet XL 50–60 mg Summary of Product Characteristics. Last updated 17 June 2014. Last accessed January 2015.
  15. Aderall XR Product Monograph, Canada. Last updated 7 January 2015. Last accessed March 2015.
  16. Elvanse Summary of Product Characteristics. Last updated 07 January 2015. Last accessed January 2015.
  17. Strattera Summary of Product Characteristics. Last updated 19 December 2013. Last accessed March 2015.
  18. Canadian Intuniv Prescribing Information. Shire Canada Inc. Last updated 23 January 2015. Last accessed May 2015.
  19. Wilens TE. Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2008; 28(3 Suppl 2): S46-53.
  20. Hodgkins P, Shaw M, McCarthy S, et al. The pharmacology and clinical outcomes of amphetamines to treat ADHD. CNS Drugs 2012; 26: 245-268.
  21. Rang HP, Dale MM, Ritter JM. Central nervous system stimulants and psychotomimetic drugs in: Pharmacology. Edinburgh: Churchill Livingstone, 2009; 603-613.
  22. Bymaster FP, Katner JS, Nelson DL, et al. Atomoxetine increases extracellular levels of noprepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology 2002; 27: 699-711.
  23. Wang M, Ramos BP, Paspalas CD, et al. Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex. Cell 2007; 129: 397-410.
  24. Ji XH, Ji JZ, Zhang H, et al. Stimulation of alpha2-adrenoceptors suppresses excitatory synaptic transmission in the medial prefrontal cortex of rat. Neuropsychopharmacology 2008; 33: 2263-2271.
  25. Yi F, Liu SS, Luo F, et al. Signaling mechanism underlying alpha2A-adrenergic suppression of excitatory synaptic transmission in the medial prefrontal cortex of rats. Eur J Neurosci 2013; 38: 2364-2373.

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