Research and Clinical Trials on Guanfacine (Tenex)

By Dr Greg Mulhauser
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This list of current clinical research trials on Guanfacine (Tenex) is followed by a short set of abstracts from the most recent research articles published on the drug.

Article Contents

Guanfacine (Tenex) Clinical Research Trials

From our searchable database at ClinicalTrialsFeeds.org, this list includes all the latest information about clinical trials involving Guanfacine (Tenex).

 

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Current Research Literature on Guanfacine (Tenex)

Here are abstracts for some of the latest research articles to have appeared on Guanfacine (Tenex):

Guanfacine in Children with Autism and/or Intellectual Disabilities.

J Dev Behav Pediatr. 2008 Jun 12;
Handen BL, Sahl R, Hardan AY
OBJECTIVE:: Attention-deficit/hyperactivity disorder (ADHD) affects 3%-5% of typical school-age children. However, considerably higher rates of ADHD (15%-25%) are observed in children with intellectual disability and autism. Studies of psychostimulants in the latter two populations have found poorer response rates compared to typically developing children. In addition, evidence suggests that children with developmental disabilities experience higher rates of adverse events. Guanfacine, an alpha2-adrenergic receptor agonist, has shown some promise as an alternative to psychostimulants. METHODS:: The present study involved a double-blind, placebo-controlled, crossover trial of guanfacine in 11 children (ages 5-9 years) with developmental disabilities and symptoms of inattention/overactivity. The 6-week trial involved a maximum dose of 3 mg/day of guanfacine. RESULTS:: Significant benefits were observed on the Hyperactivity subscale of the parent and teacher Aberrant Behavior Checklist (ABC) and Global Improvement Ratings. No gains were noted on other ABC subscales. Five of the 11 subjects (45%) were judged to be responders based on a 50% decrease in the ABC Hyperactivity subscale score between the placebo and guanfacine conditions. Several side effects were reported, including drowsiness and irritability. CONCLUSION:: While guanfacine appears to be an alternative to psychostimulants among children with developmental disabilities, clinicians need to remain vigilant to the possibility of side effects.

Partial agonism at the human alpha(2A)-autoreceptor: role of binding duration.

Naunyn Schmiedebergs Arch Pharmacol. 2008 Jul; 378(1): 17-26
Hoeren M, Brawek B, Mantovani M, Löffler M, Steffens M, van Velthoven V, Feuerstein TJ
Temperature-induced changes of affinity and efficacy of the alpha(2)-adrenoceptor full agonist UK14,304 and the partial agonists clonidine and guanfacine were investigated to elucidate the mechanism of partial agonism at the terminal alpha(2)-autoreceptor. The effect of temperature on the efficacy of the substances was tested in (3)H-noradrenaline release experiments at 37 degrees C and at room temperature. Human neocortical slices were prelabeled with (3)H-noradrenaline, superfused, and stimulated electrically under autoinhibition-free conditions. Furthermore, saturation binding experiments with human neocortical synaptosomes were performed at 37 degrees C and 17 degrees C to evaluate the influence of temperature on the affinity of (3)H-clonidine and (3)H-UK14,304. Temperature-induced changes of the association and dissociation rate constants of (3)H-UK14,304 and (3)H-clonidine were assessed in corresponding kinetic binding experiments. Our experiments reveal that clonidine and guanfacine lose efficacy when the temperature is lowered, whereas no change was noted for the full agonist UK14,304. Moreover, the affinity of clonidine and guanfacine was shown to decrease at lower temperature. Kinetic experiments indicated that the loss of affinity observed for (3)H-clonidine at 17 degrees C is due to a marked reduction of the association rate. The loss of efficacy of the partial agonists is most likely related to the short binding duration; partial agonists do not bind long enough to the receptor to mediate a maximum response. The discrepancy between the time required to elicit a maximum response and the actual binding time may be greater for partial agonists at lower temperatures, thus, causing the intrinsic activity to decline.

A placebo-controlled trial of guanfacine for the treatment of posttraumatic stress disorder in veterans.

Psychopharmacol Bull. 2008; 41(1): 8-18
Davis LL, Ward C, Rasmusson A, Newell JM, Frazier E, Southwick SM
Preclinical and clinical studies demonstrate a hyperactivity of the norepinephrine system in patients with posttraumatic stress disorder (PTSD). a(2) adrenergic agonists have been shown to ameliorate symptoms of PTSD, likely because of their ability to dampen noradrenergic tone. This study tests the ability of the a(2) adrenergic agonist, guanfacine, to reduce the symptoms of PTSD. Experimental Design: Patients with chronic PTSD were randomized (1:1) to an 8-week double-blind, placebo-controlled treatment of guanfacine followed by a 2 month open label extension phase. Patients were maintained on their stable doses of allowed antidepressants during the trial. Efficacy was measured by the following assessment scales: Clinician Administered PTSD Scale (CAPS), Montgomery Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement (CGI-I), and Davidson Trauma Scale (DTS, self-report). Principal Observations: There were no significant differences in the drug versus placebo responses for the clinician-administered or patient self-report outcome measures in this small sample of predominantly male combat veterans with PTSD. However, the medication was well tolerated. Similar to previous findings, this small pilot study failed to show differences in the response to guanfacine versus placebo in a small sample of predominantly male combat veterans with PTSD.

Inhibition of opioid release in the rat spinal cord by alpha2C adrenergic receptors.

Neuropharmacology. 2008 May; 54(6): 944-53
Chen W, Song B, Marvizón JC
Neurotransmitter receptors that control the release of opioid peptides in the spinal cord may play an important role in pain modulation. Norepinephrine, released by a descending pathway originating in the brainstem, is a powerful inducer of analgesia in the spinal cord. Adrenergic alpha2C receptors are present in opioid-containing terminals in the dorsal horn, where they could modulate opioid release. The goal of this study was to investigate this possibility. Opioid release was evoked from rat spinal cord slices by incubating them with the sodium channel opener veratridine in the presence of peptidase inhibitors (actinonin, captopril and thiorphan), and was measured in situ through the internalization of mu-opioid receptors in dorsal horn neurons. Veratridine produced internalization in 70% of these neurons. The alpha2 receptor agonists clonidine, guanfacine, medetomidine and UK-14304 inhibited the evoked mu-opioid receptor internalization with IC50s of 1.7 microM, 248 nM, 0.3 nM and 22 nM, respectively. However, inhibition by medetomidine was only partial, and inhibition by UK-14304 reversed itself at concentrations higher than 50 nM. None of these agonists inhibited mu-opioid receptor internalization produced by endomorphin-2, showing that they inhibited opioid release and not the internalization itself. The inhibitions produced by clonidine, guanfacine or UK-14304 were completely reversed by the selective alpha2C antagonist JP-1203. In contrast, inhibition by guanfacine was not prevented by the alpha2A antagonist BRL-44408. These results show that alpha2C receptors inhibit the release of opioids in the dorsal horn. This action may serve to shut down the opioid system when the adrenergic system is active.

Pharmacological and therapeutic directions in ADHD: Specificity in the PFC.

Behav Brain Funct. 2008; 4: 12
Levy F
ABSTRACT: BACKGROUND: Recent directions in the treatment of ADHD have involved both a broadening of pharmacological perspectives to include nor-adrenergic as well as dopaminergic agents. A review of animal and human studies of pharmacological and therapeutic directions in ADHD suggests that the D1 receptor is a specific site for dopaminergic regulation of the PFC, but optimal levels of dopamine (DA) are required for beneficial effects on working memory. Animal and human studies indicate that the alpha-2A receptor is also important for prefrontal regulation, leaving open the question of the relative importance of these receptor sites. The therapeutic effects of ADHD medications in the prefrontal cortex have focused attention on the development of working memory capacity in ADHD. HYPOTHESIS: The actions of dopaminergic vs noradrenergic agents, currently available for the treatment of ADHD have overlapping, but different actions in the prefrontal cortex (PFC) and subcortical centers. While stimulants act on D1 receptors in the dorsolateral prefrontal cortex, they also have effects on D2 receptors in the corpus striatum and may also have serotonergic effects at orbitofrontal areas. At therapeutic levels, dopamine (DA) stimulation (through DAT transporter inhibition) decreases noise level acting on subcortical D2 receptors, while NE stimulation (through alpha-2A agonists) increases signal by acting preferentially in the PFC possibly on DAD1 receptors. On the other hand, alpha-2A noradrenergic transmission is more limited to the prefrontal cortex (PFC), and thus less likely to have motor or stereotypic side effects, while alpha-2B and alpha-2C agonists may have wider cortical effects. The data suggest a possible hierarchy of specificity in the current medications used in the treatment of ADHD, with guanfacine likely to be most specific for the treatment of prefrontal attentional and working memory deficits. Stimulants may have broader effects on both vigilance and motor impulsivity, depending on dose levels, while atomoxetine may have effects on attention, anxiety, social affect, and sedation via noradrenergic transmission. TESTS OF THE HYPOTHESIS: At a theoretical level, the advent of possible specific alpha-2A noradrenergic therapies has posed the question of the role of working memory in ADHD. Head to head comparisons of stimulant and noradrenergic alpha-2A, alpha-2B and alpha-2C agonists, utilizing vigilance and affective measures should help to clarify pharmacological and therapeutic differences.

 

This page was last reviewed by Dr Greg Mulhauser, Friday, 4 July 2008.

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http://counsellingresource.com/medications/trials-and-research/guanfacine-research.html