Guanfacine, sold under the brand name Tenex (immediate-release) and Intuniv (extended-release) among others, is an oral alpha-2a agonist medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure.

[15] Guanfacine (as brand name Intuniv) is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications.

[30] Common (1–10% incidence) adverse effects include decreased appetite, nausea, dry mouth, urinary incontinence, and rashes.

[31][32] A 2020 systematic review found side effects of guanfacine including abdominal pain, sedation, and QT prolongation.

Medications that inhibit or induce those enzymes change the amount of guanfacine in circulation and thus its efficacy and rate of adverse effects.

[42] In ADHD, guanfacine is thought to work by strengthening the regulation of attention and behavior by the prefrontal cortex.

[43][18] These enhancing effects on prefrontal cortical functions are believed to be due to drug stimulation of post-synaptic α2A-adrenoceptors on dendritic spines, and are not dependent on activation of pre-synaptic α2A-adrenoceptors.

[18] Cyclic adenosine monophosphate (cAMP)-mediated opening of HCN and KCNQ channels is inhibited, which enhances prefrontal cortical synaptic connectivity and neuronal firing.

[43][44] In monkeys, guanfacine improves working memory, attention regulation, and behavioral inhibition, and these actions are independent of its sedative effects.

[45] Guanfacine has been found to act as a full agonist of the trace amine-associated receptor 1 (TAAR1) with an EC50Tooltip half-maximal effective concentration and EmaxTooltip maximal efficacy of 20 nM and ≥85% respectively.

As such, metabolism by the liver is the assumption for those with impaired renal function, as supported by the increased frequency of known side effects of orthostatic hypotension and sedation.

[60] In 2010, guanfacine was approved by the FDA for the treatment of attention deficit hyperactivity disorder for people 6 to 17 years old.

[63] Brand names include Tenex, Afken, Estulic, and Intuniv (an extended release formulation).

Evidence of efficacy in adults is limited, but one study found positive results in children with comorbid ADHD.

[67] Guanfacine has been shown to help reduce stress-induced craving of nicotine in smokers trying to quit, which may involve strengthening of prefrontal cortex-mediated self-control.

[68] Guanfacine has been researched for treatment of a variety of conditions impacting prefrontal cortex function, including cognitive and attentional problems in people with traumatic brain injury, stroke, schizophreniform disorders, and the elderly.