주의력결핍 과잉행동장애 치료제 개발을 위한 카테콜아민계 표적화 = Targeting Catecholamines to Develop New Drugs for Attention Deficit Hyperactivity Disorder

다국어 초록 (Multilingual Abstract)

The prevalence of attention deficit hyperactivity disorder (ADHD), a developmental neuropsychiatric disorder, is high among children and adolescents. The pathogenesis of ADHD is mediated with genetic, biological, and environmental factors. Most therapeutic drugs for ADHD have so far targeted biological causes, primarily by regulating catecholaminergic neurotransmitters. However, ADHD drugs that are clinically treated have various problems in their addictiveness and drug stability; thus, it is recommended that efficacy and safety should be secured through simultaneous prescription of multiple drugs rather than a single drug treatment. Accordingly, it is necessary to develop drugs that newly target pathogenic mechanisms of ADHD. In this study, we attempt to confirm the possibility of developing new drugs by reviewing dopaminerelated developmental mechanisms of neurons and their correlation with ADHD. Histone deacetylase inhibitors (HDACi) can regulate the concentration of intracellular dopamine in neurons by expressing vesicular monoamine transporter 2 and inducing the exocytosis of neurotransmitters to the synaptic cleft, thereby promoting the development of neurons and signal transmission. This cellular modulation of HDACi is expected to treat ADHD by regulating endogenous catecholamines such as dopamine. Although studies are still in the preclinical stage, HDAC inhibitors clearly have potential as a therapeutic agent with low addictiveness and high efficacy for ADHD treatment.

참고문헌 (Reference)

1 권국주, "성인 주의력결핍과잉행동장애의 약물치료" 대한의사협회 64 (64): 49-56, 2021

2 Biederman J, "Young adult outcome of attention deficit hyperactivity disorder : a controlled 10-year follow-up study" 36 : 167-179, 2006

3 Lohr KM, "VMAT2 and Parkinson’s disease : harnessing the dopamine vesicle" 14 : 1115-1117, 2014

4 Kimijima H, "Trichostatin A, a histone deacetylase inhibitor, alleviates the emotional abnormality induced by maladaptation to stress in mice" 766 : 136340-, 2022

5 Weissenberger S, "Time perception is a focal symptom of attention-deficit/hyperactivity disorder in adults" 27 : e933766-, 2021

6 Zia A, "The role of curcumin in aging and senescence : Molecular mechanisms" 134 : 111119-, 2021

7 Pliszka SR, "The Texas children’s medication algorithm project : revision of the algorithm for pharmacotherapy of attention-deficit/hyperactivity disorder" 45 : 642-657, 2006

8 Purves-Tyson TD, "Testosterone induces molecular changes in dopamine signaling pathway molecules in the adolescent male rat nigrostriatal pathway" 9 : e91151-, 2014

9 The Korean Academy of Child and Adolescent Psychiatry, "Survey of adult ADHD: recognition and treatment status" The Korean Academy of Child and Adolescent Psychiatry

10 Khattar JA, "Supernus announces FDA approval of Qelbree ™ (SPN-812) for the treatment of ADHD" Supernus Pharmaceuticals, Inc

11 Ershadi ASB, "SAHA improves depressive symptoms, cognitive impairment and oxidative stress: rise of a new antidepressant class" 46 : 1252-1263, 2021

12 Ramirez AD, "Regulation of dopamine signaling in the striatum by phosphodiesterase inhibitors : novel therapeutics to treat neurological and psychiatric disorders" 14 : 72-82, 2014

13 Govindarajan N, "Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer’s disease" 5 : 52-63, 2013

14 van Wingen GA, "Reduced striatal brain volumes in non-medicated adult ADHD patients with comorbid cocaine dependence" 131 : 198-203, 2013

15 Zhang L, "Recent progress in the development of histone deacetylase inhibitors as anti-cancer agents" 13 : 1999-2013, 2013

16 Buske-Kirschbaum A, "Psychoendocrine and psychoneuroimmunological mechanisms in the comorbidity of atopic eczema and attention deficit/hyperactivity disorder" 38 : 12-23, 2013

17 Sobanski E, "Psychiatric comorbidity and functional impairment in a clinically referred sample of adults with attention-deficit/hyperactivity disorder(ADHD)" 257 : 371-377, 2007

18 Fatima M, "Prenatal stress and depression associated neuronal development in neonates" 60 : 1-7, 2017

19 Lautarescu A, "Prenatal stress : effects on fetal and child brain development" 150 : 17-40, 2020

20 Sang-Chan Jeon, "Prenatal Exposure to High Cortisol Induces ADHD-like Behaviors with Delay in Spatial Cognitive Functions during the Post-weaning Period in Rats" 한국뇌신경과학회 30 (30): 87-100, 2021

21 Zalsman G, "Platelet vesicular monoamine transporter 2 density in the disruptive behavior disorders" 21 : 341-344, 2011

22 Iijima M, "Pharmacological characterization of repeated corticosterone injection-induced depression model in rats" 1359 : 75-80, 2010

23 Wehry AM, "Pharmacogenomic testing in child and adolescent psychiatry : an evidence-based review" 48 : 40-49, 2018

24 Bogi E, "Perinatal exposure to venlafaxine leads to lower anxiety and depression-like behavior in the adult rat offspring" 29 : 445-452, 2018

25 Joseph N, "Oxidative stress and ADHD : a meta-analysis" 19 : 915-924, 2015

26 Storebø OJ, "Methylphenidate for attention deficit hyperactivity disorder(ADHD)in children and adolescents-assessment of adverse events in non-randomised studies" 5 : CD012069-, 2018

27 Johnson AC, "Memory impairment in spontaneously hypertensive rats is associated with hippocampal hypoperfusion and hippocampal vascular dysfunction" 40 : 845-859, 2020

28 Slopen N, "Maternal experiences of intimate partner violence and C-reactive protein levels in young children in Tanzania" 6 : 107-115, 2018

29 Raz L, "MMP-9 inhibitors impair learning in spontaneously hypertensive rats" 13 : e0208357-, 2018

30 Bairos-Novak KR, "Like mother, like daughter: heritability of female Richardson’s ground squirrel Urocitellus richardsonii cortisol stress responses" 64 : 153-163, 2018

31 Rando J, "KemPharm announces FDA approval of AZSTARYS™ (serdexmethylphenidate and dexmethylphenidate capsules, for oral use, CII), a new once-daily treatment for ADHD" KemPharm

32 Lorenzo-Sanz G, "Involvement of vesicular monoamine transporter in attention deficit hyperactivity disorder" 52 (52): S103-S108, 2011

33 World Health Organization, "International classification of diseases 11th revision (ICD-11)" World Health Organization

34 Sezen H, "Increased oxidative stress in children with attention deficit hyperactivity disorder" 21 : 248-253, 2016

35 Ma K, "Histone deacetylase inhibitor MS-275 restores social and synaptic function in a Shank3-deficient mouse model of autism" 43 : 1779-1788, 2018

36 Keresztes A, "Hair cortisol concentrations are associated with hippocampal subregional volumes in children" 10 : 4865-, 2020

37 Lopez-Atalaya JP, "Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition" 41 : 8072-8084, 2013

38 Gong Y, "Female early adult depression results in detrimental impacts on the behavioral performance and brain development in offspring" 18 : 461-470, 2012

39 Swales DA, "Exposure to traumatic events in childhood predicts cortisol production among high risk pregnant women" 139 : 186-192, 2018

40 Mateos RM, "Excess hydrocortisone hampers placental nutrient uptake disrupting cellular metabolism" 2018 : 5106174-, 2018

41 Kim J, "Effects of high-frequency repetitive transcranial magnetic stimulation (rTMS)on spontaneously hypertensive rats, an animal model of attention-deficit/hyperactivity disorder" 53 : 83-89, 2016

42 Pervanidou P, "Early-life stress : from neuroendocrine mechanisms to stress-related disorders" 89 : 372-379, 2018

43 Takai Y, "Early-life photoperiod influences depression-like behavior, prepulse inhibition of the acoustic startle response, and hippocampal astrogenesis in mice" 374 : 133-143, 2018

44 Burbulla LF, "Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease" 357 : 1255-1261, 2017

45 Banerjee K, "Dopamine cytotoxicity involves both oxidative and nonoxidative pathways in SH-SY5Y cells : potential role of alpha-synuclein overexpression and proteasomal inhibition in the etiopathogenesis of Parkinson’s disease" 2014 : 878935-, 2014

46 Kozłowska A, "Differences in serum steroid hormones concentrations in spontaneously hypertensive rats(SHR)-an animal model of attention-deficit/hyperactivity disorder(ADHD)" 68 : 25-36, 2019

47 Cunill R, "Clinical practice guideline on pharmacological and psychological management of adult patients with attention deficit and hyperactivity disorder and comorbid substance use" 2021

48 Health Insurance Review & Assessment Service, "Children and adolescent attention deficit hyperactivity disorder" Health Insurance Review & Assessment Service

49 Grünblatt E, "Characterization of cognitive deficits in spontaneously hypertensive rats, accompanied by brain insulin receptor dysfunction" 3 : 6-, 2015

50 Wyciszkiewicz A, "Cerebellar volume in children with attention-deficit hyperactivity disorder(ADHD)" 32 : 215-221, 2017

51 de Bartolomeis A, "Calcium-dependent networks in dopamine-glutamate interaction : the role of postsynaptic scaffolding proteins" 46 : 275-296, 2012

52 Loke H, "Biological factors underlying sex differences in neurological disorders" 65 : 139-150, 2015

53 Nazzari S, "Beyond the HPA-axis : exploring maternal prenatal influences on birth outcomes and stress reactivity" 101 : 253-262, 2019

54 Blum K, "Attention-deficit-hyperactivity disorder and reward deficiency syndrome" 4 : 893-918, 2008

55 Molina BSG, "Adolescents treated for attention-deficit/hyperactivity disorder in pediatric primary care : characterizing risk for stimulant diversion" 42 : 540-552, 2021

56 Szewczyk B, "Activation of mTOR dependent signaling pathway is a necessary mechanism of antidepressant-like activity of zinc" 99 : 517-526, 2015