Lack of Effects of Guanfacine on Executive and Memory Functions in Healthy Male Volunteers

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2005 Aug 4

PMID 16078088

Citations 29

Authors

Ulrich Muller

Luke Clark

Minh L Lam

Rebecca M Moore

C Louise Murphy

Nicola K Richmond

Ranbir S Sandhu

Ingrid A Wilkins

David K Menon

Barbara J Sahakian

Trevor W Robbins

Affiliations

Soon will be listed here.

Abstract

Rationale: Guanfacine is an alpha2-adrenergic receptor agonist that has been shown to have beneficial effects on working memory and attentional functions in monkeys and in patients with attention deficit hyperactivity disorder.

Objectives: The aim of this study was to further investigate the cognitive-enhancing properties of guanfacine using an established battery of tasks measuring executive and memory functions.

Methods: Sixty healthy male volunteers were randomised into three groups. Cognitive testing was performed from +2 to +4 h after double-blind administration of a single oral dose of 1 or 2 mg of guanfacine or placebo.

Results: Systolic blood pressure was significantly reduced by both doses of guanfacine at the end of the testing session. There were no statistically significant effects on any of the cognitive measures. Two trend effects were observed with poorer performance on digit span backward and slower 'Go' reaction times after guanfacine.

Conclusion: This study found no improvement of prefrontal memory or executive functions after guanfacine. Negative effects on blood pressure and trend effects on digit span backward and go reaction time indicate a mild sedative effect of guanfacine at these doses, possibly via mechanisms of autoreceptor down-regulation.

Citing Articles

Executive Function Outcome of Treatment with Viloxazine Extended-Release Capsules in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Post-Hoc Analysis of Four Randomized Clinical Trials.

Faraone S, Gomeni R, Hull J, Busse G, Melyan Z, Rubin J Paediatr Drugs. 2021; 23(6):583-589.

PMID: 34523063 PMC: 8563661. DOI: 10.1007/s40272-021-00470-2.

Sex differences in noradrenergic modulation of attention and impulsivity in rats.

Mei X, Wang L, Yang B, Li X Psychopharmacology (Berl). 2021; 238(8):2167-2177.

PMID: 33834255 DOI: 10.1007/s00213-021-05841-8.

Guanfacine's mechanism of action in treating prefrontal cortical disorders: Successful translation across species.

Arnsten A Neurobiol Learn Mem. 2020; 176:107327.

PMID: 33075480 PMC: 7567669. DOI: 10.1016/j.nlm.2020.107327.

(Lack of) Effects of noradrenergic stimulation on human working memory performance.

Wanke N, Muller J, Wiedemann K, Schwabe L Psychopharmacology (Berl). 2020; 237(10):3033-3046.

PMID: 32583013 PMC: 7524848. DOI: 10.1007/s00213-020-05590-0.

Effect of ADHD medication in male C57BL/6J mice performing the rodent Continuous Performance Test.

Caballero-Puntiverio M, Lerdrup L, Grupe M, Larsen C, Dietz A, Andreasen J Psychopharmacology (Berl). 2019; 236(6):1839-1851.

PMID: 30656365 DOI: 10.1007/s00213-019-5167-x.

References

Middleton H, Sharma A, Agouzoul D, Sahakian B, Robbins T . Idazoxan potentiates rather than antagonizes some of the cognitive effects of clonidine. Psychopharmacology (Berl). 1999; 145(4):401-11. DOI: 10.1007/s002130051074. View

Morrow B, George T, Roth R . Noradrenergic alpha-2 agonists have anxiolytic-like actions on stress-related behavior and mesoprefrontal dopamine biochemistry. Brain Res. 2004; 1027(1-2):173-8. DOI: 10.1016/j.brainres.2004.08.057. View

Owen A, Downes J, Sahakian B, Polkey C, Robbins T . Planning and spatial working memory following frontal lobe lesions in man. Neuropsychologia. 1990; 28(10):1021-34. DOI: 10.1016/0028-3932(90)90137-d. View

Ernst M, Kimes A, London E, Matochik J, Eldreth D, Tata S . Neural substrates of decision making in adults with attention deficit hyperactivity disorder. Am J Psychiatry. 2003; 160(6):1061-70. DOI: 10.1176/appi.ajp.160.6.1061. View

Coull J, Jones M, Egan T, Frith C, Maze M . Attentional effects of noradrenaline vary with arousal level: selective activation of thalamic pulvinar in humans. Neuroimage. 2004; 22(1):315-22. DOI: 10.1016/j.neuroimage.2003.12.022. View

Cornish L . Guanfacine hydrochloride: a centrally acting antihypertensive agent. Clin Pharm. 1988; 7(3):187-97. View

Jakala P, Sirvio J, Riekkinen M, Koivisto E, Kejonen K, Vanhanen M . Guanfacine and clonidine, alpha 2-agonists, improve paired associates learning, but not delayed matching to sample, in humans. Neuropsychopharmacology. 1999; 20(2):119-30. DOI: 10.1016/S0893-133X(98)00055-4. View

Biederman J, Spencer T, Wilens T . Evidence-based pharmacotherapy for attention-deficit hyperactivity disorder. Int J Neuropsychopharmacol. 2004; 7(1):77-97. DOI: 10.1017/S1461145703003973. View

Barch D . Pharmacological manipulation of human working memory. Psychopharmacology (Berl). 2004; 174(1):126-35. DOI: 10.1007/s00213-003-1732-3. View

10.

Franowicz J, Arnsten A . Actions of alpha-2 noradrenergic agonists on spatial working memory and blood pressure in rhesus monkeys appear to be mediated by the same receptor subtype. Psychopharmacology (Berl). 2002; 162(3):304-12. DOI: 10.1007/s00213-002-1110-6. View

11.

Wang M, Ji J, Li B . The alpha(2A)-adrenergic agonist guanfacine improves visuomotor associative learning in monkeys. Neuropsychopharmacology. 2003; 29(1):86-92. DOI: 10.1038/sj.npp.1300278. View

12.

Overtoom C, Verbaten M, Kemner C, Kenemans J, van Engeland H, Buitelaar J . Effects of methylphenidate, desipramine, and L-dopa on attention and inhibition in children with Attention Deficit Hyperactivity Disorder. Behav Brain Res. 2003; 145(1-2):7-15. DOI: 10.1016/s0166-4328(03)00097-4. View

13.

Mehta M, Goodyer I, Sahakian B . Methylphenidate improves working memory and set-shifting in AD/HD: relationships to baseline memory capacity. J Child Psychol Psychiatry. 2004; 45(2):293-305. DOI: 10.1111/j.1469-7610.2004.00221.x. View

14.

Aron A, Dowson J, Sahakian B, Robbins T . Methylphenidate improves response inhibition in adults with attention-deficit/hyperactivity disorder. Biol Psychiatry. 2003; 54(12):1465-8. DOI: 10.1016/s0006-3223(03)00609-7. View

15.

Manes F, Sahakian B, Clark L, Rogers R, Antoun N, Aitken M . Decision-making processes following damage to the prefrontal cortex. Brain. 2002; 125(Pt 3):624-39. DOI: 10.1093/brain/awf049. View

16.

Robbins T, James M, Owen A, Sahakian B, Lawrence A, McInnes L . A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: implications for theories of executive functioning and cognitive aging. Cambridge Neuropsychological Test Automated.... J Int Neuropsychol Soc. 1998; 4(5):474-90. DOI: 10.1017/s1355617798455073. View

17.

Arnsten A, Cai J, Goldman-Rakic P . The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes. J Neurosci. 1988; 8(11):4287-98. PMC: 6569464. View

18.

Marien M, Colpaert F, Rosenquist A . Noradrenergic mechanisms in neurodegenerative diseases: a theory. Brain Res Brain Res Rev. 2004; 45(1):38-78. DOI: 10.1016/j.brainresrev.2004.02.002. View

19.

Sagar H . Clinicopathological heterogeneity and non-dopaminergic influences on behavior in Parkinson's disease. Adv Neurol. 1999; 80:409-17. View

20.

Norris H . The action of sedatives on brain stem oculomotor systems in man. Neuropharmacology. 1971; 10(21):181-91. DOI: 10.1016/0028-3908(71)90039-6. View