The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder

Abstract

Neuropsychiatric disorders involve dysfunction of the prefrontal cortex (PFC), a highly evolved brain region that mediates executive functioning. The dorsolateral PFC is specialized for regulating attention and behavior, while the ventromedial PFC is specialized for regulating emotion. These abilities arise from PFC pyramidal cell networks that excite each other to maintain goals and rules ‘in mind’. Imaging studies have shown reduced PFC gray matter, weaker PFC connections and altered PFC function in patients with attention-deficit/hyperactivity disorder. Thus, medications that strengthen PFC network connections may be particularly useful for the treatment of attention-deficit/hyperactivity disorder and related disorders. Recent data show that compounds such as guanfacine can enhance PFC function by stimulating postsynaptic α-2A receptors on the dendritic spines of PFC pyramidal cells where networks interconnect. Stimulation of these receptors inhibits cAMP signaling, thus closing potassium channels and strengthening physiological connections. These actions may benefit patients with weak PFC function.

Keywords::

• α-2A adrenoceptors
• attention-deficit/hyperactivity disorder
• benzedrine
• cAMP signaling
• clonidine
• dopamine
• guanfacine
• norepinephrine
• prefrontal cortex
• stimulations

Financial & competing interests disclosure

Amy Arnsten and Yale University receive royalties from Shire Pharmaceuticals from the sales of extended-release guanfacine (Intuniv^TM) for the treatment of ADHD and related disorders. Dr Arnsten consults and engages in teaching for Shire, and receives research funding from Shire for the study of catecholamine mechanisms in the prefrontal cortex. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.