Browsing by Subject "Guanfacine"

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    Guanfacine and guanfacine extended release: treatment for ADHD and related disorders
    (Wiley, 2007) Posey, David J.; McDougle, Christopher J.; Psychiatry, School of Medicine
    Guanfacine, an alpha(2A) adrenoceptor agonist, is U.S. Food and Drug Administration (FDA)-approved for the treatment of hypertension in adolescents and adults. It also has been used "off-label" for several years in children as a possible treatment for attention-deficit/hyperactivity disorder (ADHD) and pervasive developmental disorders (PDDs). Small placebo-controlled trials support the use of guanfacine for the treatment of ADHD. There is more limited research on the use of guanfacine in treating hyperactivity occurring in children diagnosed with PDD. Recently, guanfacine extended release (GXR), a once-daily formulation has been manufactured and studied in phase III clinical trials. Based on preliminary scientific presentations, it also appears to be efficacious in improving ADHD in children. The most common adverse effects associated with guanfacine and GXR treatment is sedation. Adverse cardiovascular effects are uncommon, although modest reductions in blood pressure and heart rate are common. If GXR is FDA-approved, it would be the first alpha(2A) adrenoceptor agonist marketed for ADHD.
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    Guanfacine treatment improves ADHD phenotypes of impulsivity and hyperactivity in a neurofibromatosis type 1 mouse model
    (BMC, 2020-01-15) Lukkes, J. L.; Drozd, H. P.; Fitz, S. D.; Molosh, A. I.; Clapp, D. W.; Shekhar, A.; Psychiatry, School of Medicine
    BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a mutation in one copy of the neurofibromin gene (NF1+/-). Even though approximately 40-60% of children with NF1 meet the criteria for attention deficit hyperactivity disorder (ADHD), very few preclinical studies, if any, have investigated alterations in impulsivity and risk-taking behavior. Mice with deletion of a single NF1 gene (Nf1+/-) recapitulate many of the phenotypes of NF1 patients. METHODS: We compared wild-type (WT) and Nf1+/- mouse strains to investigate differences in impulsivity and hyperactivity using the delay discounting task (DDT), cliff avoidance reaction (CAR) test, and open field. We also investigated whether treatment with the clinically effective alpha-2A adrenergic receptor agonist, guanfacine (0.3 mg/kg, i.p.), would reverse deficits observed in behavioral inhibition. RESULTS: Nf1+/- mice chose a higher percentage of smaller rewards when both 10- and 20-s delays were administered compared to WT mice, suggesting Nf1+/- mice are more impulsive. When treated with guanfacine (0.3 mg/kg, i.p.), Nf1+/- mice exhibited decreased impulsive choice by waiting for the larger, delayed reward. Nf1+/- mice also exhibited deficits in behavioral inhibition compared to WT mice in the CAR test by repetitively entering the outer edge of the platform where they risk falling. Treatment with guanfacine ameliorated these deficits. In addition, Nf1+/- mice exhibited hyperactivity as increased distance was traveled compared to WT controls in the open field. This hyperactivity in Nf1+/- mice was reduced with guanfacine pre-treatment. CONCLUSIONS: Overall, our study confirms that Nf1+/- mice exhibit deficits in behavioral inhibition in multiple contexts, a key feature of ADHD, and can be used as a model system to identify alterations in neural circuitry associated with symptoms of ADHD in children with NF1.