- Iridium-catalyzed enantioselective synthesis of chiral γ-amino alcohols and intermediates of (S)-duloxetine, (R)-fluoxetine, and (R)-atomoxetine. [Journal Article]
- Chiral γ-amino alcohols are the prevalent structural motifs and building blocks in pharmaceuticals and bioactive molecules. Enantioselective hydrogenation of β-amino ketones provides a straightforward and powerful tool for the synthesis of chiral γ-amino alcohols, but the asymmetric transformation is synthetically challenging. Here, a series of tridentate ferrocene-based phosphine ligands bearing…
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- Optogenetic and pharmacological interventions link hypocretin neurons to impulsivity in mice. [Journal Article]
- Neurons in the lateral hypothalamus expressing the neuropeptide Hypocretin, also known as orexin, are known critical modulators of arousal stability. However, their role in the different components of the arousal construct such as attention and decision making is poorly understood. Here we study Hypocretin neuronal circuit dynamics during stop action impulsivity in a Go/NoGo task in mice. We show…
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- [A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder: CYP2D6 genetic testing and therapeutic drug monitoring]. [Review]
- Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme…
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- Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations: A Multinational Study. [Journal Article]J Clin Psychiatry. 2023 01 16; 84(1)JC
- Objective: Most research on safety of attention-deficit/hyperactivity disorder (ADHD) medications during pregnancy concerns central nervous system stimulants, while little is known about the safety of atomoxetine, a primary treatment alternative. We assessed the prevalence of major congenital malformations overall, and cardiac malformations and limb malformations specifically, after first-trimest…
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- Reduced attentional lapses in male rats following a combination treatment of low-dose D-serine and atomoxetine. [Journal Article]J Psychopharmacol. 2023 Jan 17 [Online ahead of print]JP
- CONCLUSIONS: IT devmode is thought to reflect attentional lapses; therefore, D-serine's effects on IT devmode suggest that NMDA receptors are involved in the preparatory deployment of attention. Greater effects following a combination of D-serine and atomoxetine suggest that preparatory attention can be facilitated by targeting glutamatergic and noradrenergic systems simultaneously. These results could inform the development of improved treatments for individuals with ADHD who experience abnormally high attentional lapses.
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- Effects of Atomoxetine for the Treatment of Neurogenic Orthostatic Hypotension in Patients With Alpha-synucleinopathies: A Systematic Review of Randomized Controlled Trials and a Focus-Group Discussion. [Journal Article]J Clin Neurol. 2023 Jan 02 [Online ahead of print]JC
- CONCLUSIONS: Atomoxetine is an effective and safe option for short-term nOH management, which could be more evident in patients with central autonomic dysfunction such as MSA. However, there is a paucity of evidence in the literature, and data from the focus-group discussion were inadequate, and so further investigation is warranted.
- Personalizing atomoxetine dosing in children with ADHD: what can we learn from current supporting evidence. [Review]Eur J Clin Pharmacol. 2023 Jan 16 [Online ahead of print]EJ
- CONCLUSIONS: Personalizing atomoxetine dosage may be even more complex than anticipated thus far, but elucidating the best way to tailor the non-stimulant to a patient's individual need will be achieved by combining two strategies: detailed research in linking the pharmacokinetics and pharmacodynamics in pediatric patients, and better understanding in nature and causes of ADHD, as well as environmental stressors.
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- Drugs and Lactation Database (LactMed): Atomoxetine [BOOK]Drugs and Lactation Database (LactMed). National Library of Medicine (US): Bethesda (MD)BOOK
- There is no published experience with atomoxetine during breastfeeding, although reports from the manufacturer found no serious adverse effects in two breastfed infants. An alternate drug may be preferred, especially while nursing a newborn or preterm infant.
- Long-term treatment of adult ADHD in a naturalistic setting: clinical predictors of attrition, medication choice, improvement, and response. [Journal Article]World J Biol Psychiatry. 2023 Jan 13 [Online ahead of print]WJ
- Objectives: The aim of this study was to identify clinical predictors of treatment attrition, medication choice, improvement and response to pharmacotherapy in adult attention-deficit/hyperactivity disorder (ADHD). Methods: 150 ADHD patients were enrolled and naturalistically followed-up for at least 4 months. Conners' Adult ADHD Rating Scales-Observer: Screening Version (CAARS-O:SV) were used to…
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- One Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial. [Journal Article]Ann Am Thorac Soc. 2022 Dec 20 [Online ahead of print]AA
- CONCLUSIONS: 1 month of nightly noradrenergic and anti-muscarinic combination therapy was generally well-tolerated with a side effect profile consistent with each agent alone and was associated with an ~50% reduction from baseline in a key OSA severity metric, the hypoxic burden with the highest dose combination. These findings highlight the potential to target noradrenergic and anti-muscarinic mechanisms for OSA pharmacotherapy development.
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- New frontiers in the pharmacological treatment of social anxiety disorder in adults: an up-to-date comprehensive overview. [Journal Article]Expert Opin Pharmacother. 2022 Dec 22 [Online ahead of print]EO
- Social anxiety disorder (SAD) is associated with scarce functioning and poor quality of life. Although selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are currently first-line treatments, side effects are common and affect treatment compliance in approximately 50% of patients. This review aimed to summarize data on the efficacy of unlab…
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- Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction of CYP2D6 and COMT with atomoxetine and methylphenidate. [Journal Article]Eur J Hum Genet. 2022 Dec 12 [Online ahead of print]EJ
- Pharmacogenetics (PGx) studies the effect of heritable genetic variation on drug response. Clinical adoption of PGx has remained limited, despite progress in the field. To promote implementation, the Dutch Pharmacogenetics Working Group (DPWG) develops evidence-based guidelines on how to optimize pharmacotherapy based on PGx test results. This guideline describes optimization of atomoxetine thera…
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- Pharmacologic prevention of recurrent vasovagal syncope: A systematic review and network meta-analysis of randomized controlled trials. [Review]Heart Rhythm. 2022 Dec 09 [Online ahead of print]HR
- Vasovagal syncope (VVS) is a transient loss of consciousness that currently imposes a high burden on health care systems with limited evidence of the comparative efficacy of available pharmacologic interventions. This study aims to compare all pharmacologic therapies suggested in randomized controlled trials (RCTs) through systematic review and network meta-analysis. A systematic search in PubMed…
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- Treatment of ADHD: Drugs, psychological therapies, devices, complementary and alternative methods as well as the trends in clinical trials. [Review]
- Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders having a high influence on social interactions. The number of approved treatments and clinical trials for ADHD have increased markedly during the recent decade. This analytical review provides a quantitative overview of the existing pharmacological and non-pharmacological methods of ADHD treatme…
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- Development of pediatric orally disintegrating mini-tablets containing atomoxetine hydrochloride-β-cyclodextrin inclusion complex using experimental design. [Journal Article]Drug Dev Ind Pharm. 2022 Nov; 48(11):667-681.DD
- CONCLUSIONS: As a conclusion, the novel formulation of ODMTs with ATO/β-CD inclusion complex was successfully developed for pediatric use.
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- Meta-analysis on the efficacy of the norepinephrine reuptake inhibitors reboxetine and atomoxetine for the treatment of schizophrenia and attention deficit hyperactivity disorder. [Journal Article]Adv Clin Exp Med. 2022 Nov 30 [Online ahead of print]AC
- CONCLUSIONS: The present meta-analysis suggests that NRIs are efficacious and therefore they are potential candidate drugs for the treatment of schizophrenia and ADHD.
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- In silico analysis of the antidepressant fluoxetine and similar drugs as inhibitors of the human protein acid sphingomyelinase: a related SARS-CoV-2 inhibition pathway. [Journal Article]J Biomol Struct Dyn. 2022 Nov 29 [Online ahead of print]JB
- Acid Sphingomyelinase (ASM) is a human phosphodiesterase that catalyzes the metabolism of sphingomyelin (SM) to ceramide and phosphocholine. ASM is involved in the plasma membrane cell repair and is associated with the lysosomal inner lipid membrane by nonbonding interactions. The disruption of those interaction would result in ASM release into the lysosomal lumen and consequent degradation of it…
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- Prevalence trends and individual patterns of ADHD medication use in pregnancy in Norway and Sweden, 2010-2019. [Journal Article]
- CONCLUSIONS: ADHD medication use during pregnancy increased in Norway and Sweden in the last decade. However, discontinuation rates during pregnancy were high. Those who used ADHD medication had more risk factors for pregnancy complications including low parity, smoking, and other psychotropic drug use.
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- Theory of visual attention (TVA) applied to rats performing the 5-choice serial reaction time task: differential effects of dopaminergic and noradrenergic manipulations. [Journal Article]
- CONCLUSIONS: These data indicate that the application of TVA to the 5CSRTT provides an enhanced sensitivity to capturing attentional effects. Unexpectedly, we found overall slowing effects, including impaired visual processing, following drugs either increasing extracellular noradrenaline (atomoxetine) or activating the α1-adrenoceptor (phenylephrine), while also ameliorating premature responses (impulsivity). In contrast, amphetamine had potential pro-attentional effects by enhancing visual processing, probably due to central dopamine upregulation.
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- Assessing the nature of premature responses in the rodent continuous performance test variable intertrial interval schedule using atomoxetine and amphetamine. [Journal Article]J Neurosci Methods. 2023 Jan 15; 384:109749.JN
- CONCLUSIONS: Long ITIs increase the detectability of, but has minimal effect on, waiting impulsivity. %FiT is analogous to %PR in related tasks, while the FoT/FiT ratio is a separate behaviour requiring further characterization.
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- Atomoxetine for suppression of vasovagal syncope. [Journal Article]
- CONCLUSIONS: In this case series, atomoxetine was a promising oral agent for the prevention of vasovagal syncope. The Poisson distribution permits individual patient-level assessment of improvement and detects insufficient follow-up despite apparent improvement.
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- Novel non-stimulants rescue hyperactive phenotype in an adgrl3.1 mutant zebrafish model of ADHD. [Journal Article]
- ADHD is a highly prevalent neurodevelopmental disorder. The first-line therapeutic for ADHD, methylphenidate, can cause serious side effects including weight loss, insomnia, and hypertension. Therefore, the development of non-stimulant-based therapeutics has been prioritized. However, many of these also cause other effects, most notably somnolence. Here, we have used a uniquely powerful genetic m…
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- Atomoxetine Decreases Mitochondrial Biogenesis, Fission and Fusion In Human Neuron-like Cells But Does Not Alter Antioxidant Defences. [Journal Article]
- Atomoxetine (ATX) is a presynaptic norepinephrine transporter (NET) inhibitor widely prescribed for attention-deficit/hyperactivity disorder (ADHD) due to its low abuse potential and absence of psychostimulant effects. While NET inhibition is implicated in the clinical response, several additional pharmacoactivities may contribute to clinical efficacy or unwanted side effects. We recently reporte…
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- "Jing-Ning Granules" Can Alleviate Attention Deficit Hyperactivity Disorder in Rats by Modulating Dopaminergic D2/D1-Like Receptor-Mediated Signaling Pathways. [Journal Article]
- CONCLUSIONS: These results indicate that JNG can produce therapeutic effects by regulating the balance of D2/D1-like receptor-mediated cAMP/PKA and Ca2+/CaM/CaMKII signaling pathways.
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- Characterisation of seven medications approved for attention-deficit/hyperactivity disorder using in vitro models of hepatic metabolism. [Journal Article]Xenobiotica. 2022 Jul; 52(7):676-686.X
- The metabolism of most medications approved for the treatment of attention deficit/hyperactivity disorder (ADHD) is not fully understood.In vitro studies using cryopreserved, plated human hepatocytes (cPHHs) and pooled human liver microsomes (HLMs) were performed to more thoroughly characterise the metabolism of several ADHD medications.The use of enzyme-specific chemical inhibitors indicated a r…
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- Chondral/Desmal Osteogenesis in 3D Spheroids Sensitized by Psychostimulants. [Journal Article]
- Attention deficit hyperactivity disorder (ADHD) affects 6.4 million children in the United States of America. Children and adolescents, the main consumers of ADHD medication, are in the bone growth phase, which extends over a period of up to two decades. Thus, impaired proliferation and maturation of chondrocytes and osteoblasts can result in impaired bone formation. The aim of this study is to i…
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- Effects of Atomoxetine on Motor and Cognitive Behaviors and Brain Electrophysiological Activity of Dopamine Transporter Knockout Rats. [Journal Article]
- Changes in dopaminergic and noradrenergic transmission are considered to be the underlying cause of attention deficit and hyperactivity disorder (ADHD). Atomoxetine (ATX) is a selective norepinephrine transporter (NET) inhibitor that is currently used for ADHD treatment. In this study, we aimed to evaluate the effect of atomoxetine on the behavior and brain activity of dopamine transporter knocko…
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- Variability in the response to atomoxetine and oxybutynin for OSA: Highlighting the need for personalized medicine. [Editorial]Respirology. 2022 Oct 18 [Online ahead of print]R
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- Therapeutic Approaches for ADHD by Developmental Stage and Clinical Presentation. [Review]
- Attention Deficit Hyperactivity Disorder is a neurodevelopmental disorder with three presentations: inattentive, hyperactive/impulsive and combined. These may represent an independent disease entity. Therefore, the therapeutic approach must be focused on their neurobiological, psychological and social characteristics. To date, there is no comprehensive analysis of the efficacy of different treatm…
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- In silico analysis of the antidepressant fluoxetine and related drugs at SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro). [Journal Article]Curr Drug Discov Technol. 2022 Oct 10 [Online ahead of print]CD
- CONCLUSIONS: In an in silico perspective, it is likely that the SSRIs and other anti-depressants could interact with Mpro and cause the enzyme to malfunction. Unfortunately, the same drugs did not present similar results on PLpro crystal, therefore no inhibition is expected on an in vitro trial. Anyway, in vitro test are necessary for the better understanding the links between SARS-CoV-2 proteases and anti-depressants.
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