Has anyone had any experience with this?
I was told that dextro-amphetamine and methylphenidate elicited their
attention promoting effects through an increase in the metabolic
activity of prefrontal cortex. I was wondering whether anyone had come
across any studies that validated this.
It seems to be the widely presumed mechanism of improvement for the
executive processing function of ADHD patients receiving treatment with
these drugs. I was therefore surprised that Guanfacine was not more
widely used as a nootropic given that its effectiveness in promoting
prefrontal cortex (PFC) metabolism has been experimentally validated in
non-ADHD human controls.
Has anyone come across any studies related to improvements in prefrontal
cortex function with drug administration in ADHD patients or an
unimpaired human control group.
If this were the mechanism of a nooptropic substance it would seem easy
to validate through fMRI.
http://en.wikipedia.org/wiki/Guanfacine
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T9V-3W1YFV6-6&_user=681891&_coverDate=05%2F31%2F1999&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=681891&md5=f3421ed7315784a0d4e9e988d82689ed
Guanfacine, But Not Clonidine, Improves Planning and Working Memory
Performance in Humans
Abstract
The present study compares, using a double-blind, placebo controlled
design the effects of two α2-agonists, clonidine (0.5, 2, and 5 μg/kg)
and guanfacine (7 and 29 μg/kg) on spatial working memory, planning
and attentional set-****fting, functions thought to be dependent on the
"central executive" of the prefrontal cortex. Blood pressure and the
subjective feeling of sedation were affected equally by clonidine and
guanfacine. The 0.5 μg/kg and 5 μg/kg doses of clonidine disrupted
spatial working memory, but the medium dose had no effect. The 0.5 and
2 μg/kg doses of clonidine increased impulsive responding in the
planning test. The 5 μg/kg dose of clonidine slowed responding at
effortful levels of planning and attentional set-****fting tests. The
29 μg/kg dose of guanfacine improved spatial working memory and
planning. Guanfacine had no effect on attentional set-****fting. These
data indicate that guanfacine improved planning and spatial working
memory, but clonidine dose-dependently disrupted performance. It is
possible that the greater selectivity of guanfacine for
α2A-adrenoceptor subtype may underlie its differences from clonidine.
www.medscape.com/viewarticle/577743
(This website is worth registering for just to read this article)
The Role of Alpha 2 Agonists in the Attention Deficit/Hyperactivity
Disorder Treatment Paradigm
Floyd R. Sallee,MD
Author Information
Introduction: Why Do We Need Treatment Alternatives to Stimulants?
Attention deficit/hyperactivity disorder (ADHD) is a heterogeneous,
multifactorial disorder that can involve aspects of temperament (ie,
impulsivity), motivation (ie, reward), behavior (ie, hyperactivity),
and cognition (ie, inattention, working memory).[1-3] Although the
precise etiology of ADHD remains unknown, most effective therapies for
these diverse dimensions of the disorder facilitate catecholaminergic
transmission,[4,5] especially in the prefrontal cortex (PFC).[6]
Stimulants, the current mainstay of ADHD therapy, exhibit substantial
efficacy but this does not occur uniformly across all aspects of the
disorder. Furthermore, 25% to 35% of patients do not receive a
therapeutic benefit from stimulants because of inadequate symptom
relief, intolerable side effects, or nonadherence.[7] In this context,
alpha 2 adrenergic agonists (ie, guanfacine and clonidine) are
considered to be alternatives to stimulants based on their ability to
modulate noradrenergic tone in the PFC. This modulation is a
consequence of both enhanced noradrenergic input from the locus
coeruleus and direct postsynaptic stimulation of alpha 2A receptors.
The latter are located on dendritic spines of cortical pyramidal
cells, thereby directly promoting functional connectivity of
prefrontal cortical networks and resulting in enhanced regulation of
attention and behavior.[8] The specific and selective action of this
class of drugs to modulate noradrenergic tone in the PFC is viewed as
an essential component of their utility in specific domains of ADHD,
influencing aspects of behavior, cognition, and impulsivity in a
complementary manner to stimulants to optimize outcome, reduce
impairment, and improve functionality.
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