Viloxazine Increases Extracellular Concentrations of Norepinephrine, Dopamine, and Serotonin in the Rat Prefrontal Cortex at Doses Relevant for the Treatment of Attention-Deficit/Hyperactivity Disorder

References

• Sonuga-Barke EJS, Becker SP, Bölte S, et al. Annual research review: perspectives on progress in ADHD science – from characterization to cause. J Child Psychol Psychiatry. 2023;64(4):506–532. doi:10.1111/jcpp.13696
   PubMed Web of Science ®Google Scholar
• Popper CW. Antidepressants in the treatment of attention-deficit/hyperactivity disorder. J Clin Psychiatry. 1997;58(14):14–29.
   PubMedGoogle Scholar
• Otasowie J, Castells X, Ehimare UP, Smith CH. Tricyclic antidepressants for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2014;(9):Cd006997. doi:10.1002/14651858.CD006997.pub2
   PubMed Web of Science ®Google Scholar
• Morón JA, Brockington A, Wise RA, Rocha BA, Hope BT. Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. J Neurosci. 2002;22(2):389–395. doi:10.1523/jneurosci.22-02-00389.2002
   PubMed Web of Science ®Google Scholar
• Carlier PR, Lo MM, Lo PC, et al. Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group. Bioorg Med Chem Lett. 1998;8(5):487–492. doi:10.1016/s0960-894x(98)00062-6
   PubMed Web of Science ®Google Scholar
• Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V. New insights into the mechanism of action of viloxazine: serotonin and norepinephrine modulating properties. J Exp Pharmacol. 2020;12:285–300. doi:10.2147/jep.S256586
   PubMedGoogle Scholar
• Tatsumi M, Groshan K, Blakely RD, Richelson E. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997;340(2–3):249–258. doi:10.1016/s0014-2999(97)01393-9
   PubMed Web of Science ®Google Scholar
• Rowley HL, Kulkarni RS, Gosden J, Brammer RJ, Hackett D, Heal DJ. Differences in the neurochemical and behavioural profiles of lisdexamfetamine methylphenidate and modafinil revealed by simultaneous dual-probe microdialysis and locomotor activity measurements in freely-moving rats. J Psychopharmacol. 2014;28(3):254–269. doi:10.1177/0269881113513850
   PubMed Web of Science ®Google Scholar
• Bymaster FP, Katner JS, Nelson DL, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002;27(5):699–711. doi:10.1016/s0893-133x(02)00346-9
   PubMed Web of Science ®Google Scholar
• Koda K, Ago Y, Cong Y, Kita Y, Takuma K, Matsuda T. Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice. J Neurochem. 2010;114(1):259–270. doi:10.1111/j.1471-4159.2010.06750.x
   PubMed Web of Science ®Google Scholar
• Lippman W, Pugsley TA. Effects of viloxazine, an antidepressant agent, on biogenic amine uptake mechanisms and related activities. Can J Physiol Pharmacol. 1976;54(4):494–509. doi:10.1139/y76-069
   PubMed Web of Science ®Google Scholar
• Institute of Laboratory Animal Resources (US). Committee for the Update of the Guide for the Care and Use of Laboratory Animals IfLAR, Division on Earth and Life Studies, and National Research Council. 8 ed. Guide for the Care and Use of Laboratory Animals. National Academies Press; 2011.
   Google Scholar
• Supernus Pharmaceuticals, Inc. Qelbree [package insert]. Supernus Pharmaceuticals, Inc; 2022.
   Google Scholar
• Nasser A, Gomeni R, Wang Z, et al. Population pharmacokinetics of viloxazine extended-release capsules in pediatric subjects with attention deficit/hyperactivity disorder. J Clin Pharmacol. 2021;61(12):1626–1637. doi:10.1002/jcph.1940
   PubMed Web of Science ®Google Scholar
• Stenfors C, Ross SB. Changes in extracellular 5-HIAA concentrations as measured by in vivo microdialysis technique in relation to changes in 5-HT release. Psychopharmacology. 2004;172(2):119–128. doi:10.1007/s00213-003-1736-z
   PubMed Web of Science ®Google Scholar
• Mikail HG, Dalla C, Kokras N, Kafetzopoulos V, Papadopoulou-Daifoti Z. Sertraline behavioral response associates closer and dose-dependently with cortical rather than hippocampal serotonergic activity in the rat forced swim stress. Physiol Behav. 2012;107(2):201–206. doi:10.1016/j.physbeh.2012.06.016
   PubMed Web of Science ®Google Scholar
• Cortese S, Adamo N, Del Giovane C, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018;5(9):727–738. doi:10.1016/s2215-0366(18)30269-4
   PubMed Web of Science ®Google Scholar
• Salman T, Afroz R, Nawaz S, Mahmood K, Haleem DJ, Zarina S. Differential effects of memory enhancing and impairing doses of methylphenidate on serotonin metabolism and 5-HT1A, GABA, glutamate receptor expression in the rat prefrontal cortex. Biochimie. 2021;191:51–61. doi:10.1016/j.biochi.2021.08.009
   PubMed Web of Science ®Google Scholar
• Ding YS, Naganawa M, Gallezot JD, et al. Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: implications on treatment of depression and ADHD. NeuroImage. 2014;86:164–171. doi:10.1016/j.neuroimage.2013.08.001
   PubMed Web of Science ®Google Scholar
• Charnay Y, Léger L. Brain serotonergic circuitries. Dialogues Clin Neurosci. 2010;12(4):471–487. doi:10.31887/DCNS.2010.12.4/ycharnay
   PubMedGoogle Scholar
• Dankoski EC, Carroll S, Wightman RM. Acute selective serotonin reuptake inhibitors regulate the dorsal raphe nucleus causing amplification of terminal serotonin release. J Neurochem. 2016;136(6):1131–1141. doi:10.1111/jnc.13528
   PubMed Web of Science ®Google Scholar
• Angoa-Pérez M, Kane MJ, Briggs DI, et al. Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity. J Neurochem. 2012;121(6):974–984. doi:10.1111/j.1471-4159.2012.07739.x
   PubMed Web of Science ®Google Scholar
• Moeller FG, Dougherty DM, Swann AC, Collins D, Davis CM, Cherek DR. Tryptophan depletion and aggressive responding in healthy males. Psychopharmacology. 1996;126(2):97–103. doi:10.1007/bf02246343
   PubMed Web of Science ®Google Scholar
• Eagle DM, Lehmann O, Theobald DEH, et al. Serotonin depletion impairs waiting but not stop-signal reaction time in rats: implications for theories of the role of 5-HT in behavioral inhibition. Neuropsychopharmacology. 2009;34(5):1311–1321. doi:10.1038/npp.2008.202
   PubMed Web of Science ®Google Scholar
• Chantiluke K, Barrett N, Giampietro V, et al. Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD. Psychopharmacology. 2015;232(12):2071–2082. doi:10.1007/s00213-014-3837-2
   PubMed Web of Science ®Google Scholar
• Banerjee E, Nandagopal K. Does serotonin deficit mediate susceptibility to ADHD? Neurochem Int. 2015;82:52–68. doi:10.1016/j.neuint.2015.02.001
   PubMed Web of Science ®Google Scholar
• Martinez C, Dominiak P, Kees F, Grobecker H. Inhibition of monoamine oxidase by viloxazine in rats. Arzneimittelforschung. 1986;36(5):800–803.
   PubMed Web of Science ®Google Scholar
• Swanson CJ, Perry KW, Koch-Krueger S, Katner J, Svensson KA, Bymaster FP. Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat. Neuropharmacology. 2006;50(6):755–760. doi:10.1016/j.neuropharm.2005.11.022
   PubMed Web of Science ®Google Scholar
• Martiniova L, Cleary S, Lai EW, et al. Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma. Nucl Med Biol. 2012;39(2):215–226. doi:10.1016/j.nucmedbio.2011.07.007
   PubMed Web of Science ®Google Scholar
• Harvey RC, Sen S, Deaciuc A, Dwoskin LP, Kantak KM. Methylphenidate treatment in adolescent rats with an attention deficit/hyperactivity disorder phenotype: cocaine addiction vulnerability and dopamine transporter function. Neuropsychopharmacology. 2011;36(4):837–847. doi:10.1038/npp.2010.223
   PubMed Web of Science ®Google Scholar
• Elwan O, Adam HK. Relationship between blood and cerebrospinal levels of the antidepressant agent viloxazine. Eur J Clin Pharmacol. 1980;17(3):179–182. doi:10.1007/bf00561897
   PubMed Web of Science ®Google Scholar