Name: Guanfacine
Synonyms: Intuniv, SPD503, Afken, Estulic, Tenex
Chemical Name: N-amidino-2-(2,6dichlorophenyl) acetamide monohydrochloride
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 3)
Approved for: Attention-deficit hyperactivity disorder, hypertension


This drug is an α2A adrenergic receptor agonist. It acts in the central nervous system and is used to treat high blood pressure and attention-deficit/hyperactivity disorder (ADHD). An extended-release formulation, approved as a once-a-day medication for ADHD in children, is available as a generic. Side effects include blurred vision, confusion, faintness, sweating, fatigue, and others.

Guanfacine works in the prefrontal cortex to increase attention and cognition by activating postsynaptic norepinephrine receptors. In preclinical studies, the drug improved working memory of aged rodents and monkeys (Arnsten and Jin, 2012). People with AD show impairment in attention, which may contribute to memory problems (Malhotra, 2018). In addition, degeneration of norepinephrine-producing locus coeruleus neurons, and noradrenergic dysfunction, are recognized features of Alzheimer’s and Parkinson’s diseases (Weinshenker, 2018; Jacobs et al., 2019).


The idea that guanfacine might boost cognition in Alzheimer’s disease has been around for two decades, but not supported by trial data. The first small studies using guanfacine alone in people with AD were negative (Crook et al., 1992; Schlegel et al., 1989). Likewise, a larger trial in people with age-associated memory impairment found no benefit on learning or memory (McEntee et al., 1991). In more recent work, three months of treatment with extended-release guanfacine at one-half, and one-tenth, the dose used for ADHD did not improve attention or cognitive function in 154 healthy elderly controls (Barcelos et al., 2018).

In January 2019, a study began to evaluae guanfacine as an add-on to cholinergic treatment in people with AD. The single-center Phase 3 trial at Imperial College London is enrolling 160 participants who meet clinical criteria for probable AD and have been taking a stable dose of donepezil, galantamine, or rivastigmine for three months. They will receive 2 mg per day of extended-release guanfacine or placebo for three months. The primary outcome is performance on the ADAS-Cog; secondary outcomes include additional cognitive tests focusing on attention, plus neuropsychiatric symptoms, daily activities, and caregiver burden. Blood pressure and sleepiness will be tracked. The trial will end in early 2021. 

Guanfacine is also being studied for stress disorders, Tourette’s syndrome, and for alcohol, opioid, nicotine, or cannabis withdrawal. 

For details on guanfacine trials, see

Clinical Trial Timeline

  • Phase 3
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032
Imperial College of London NCT03116126

Last Updated: 15 Dec 2019


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Paper Citations

  1. . Noradrenergic intervention in Alzheimer's disease. Psychopharmacol Bull. 1992;28(1):67-70. PubMed.
  2. . Guanfacine treatment of Alzheimer's disease. Clin Neuropharmacol. 1989 Apr;12(2):124-8. PubMed.
  3. . Treatment of age-associated memory impairment with guanfacine. Psychopharmacol Bull. 1991;27(1):41-6. PubMed.
  4. . Guanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial. Neurobiol Aging. 2018 Oct;70:117-124. Epub 2018 May 31 PubMed.
  5. . Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale. Yale J Biol Med. 2012 Mar;85(1):45-58. Epub 2012 Mar 29 PubMed.
  6. . Impairments of attention in Alzheimer's disease. Curr Opin Psychol. 2018 Nov 8;29:41-48. PubMed.
  7. . Long Road to Ruin: Noradrenergic Dysfunction in Neurodegenerative Disease. Trends Neurosci. 2018 Apr;41(4):211-223. Epub 2018 Feb 20 PubMed.
  8. . Alzheimer's disease pathology: pathways between central norepinephrine activity, memory, and neuropsychiatric symptoms. Mol Psychiatry. 2019 May 28; PubMed.

External Citations


Further Reading


  1. . Rostral locus coeruleus integrity is associated with better memory performance in older adults. Nat Hum Behav. 2019 Sep 9; PubMed.