Objective: To evaluate the therapeutic efficacy of atomoxetine hydrochloride (ATX) combined with psychological-behavioral modification therapy for attention-deficit/hyperactivity disorder (ADHD) in children. Methods: ...Objective: To evaluate the therapeutic efficacy of atomoxetine hydrochloride (ATX) combined with psychological-behavioral modification therapy for attention-deficit/hyperactivity disorder (ADHD) in children. Methods: A total of 60 cases of ADHD children admitted to our hospital between November 2021 and November 2022 were selected and randomly grouped into Group I and Group II. There were 30 cases in Group I who were treated with ATX combined with psychological-behavioral modification therapy. There were 30 cases in Group II who were treated with ATX monotherapy, and the therapeutic effects were compared. Results: Before treatment, there was no difference in the behavioral problem scores and cognitive function indexes of the two groups (P>0.05). After treatment, the behavioral problem scores of Group I were lower than those of Group II, and the cognitive function indicators of Group I were lower than those of Group II (P < 0.05). The adverse reaction rate of Group I was lower than that of Group II, and the total effective rate was higher than that of Group II (P < 0.05). Conclusion: ATX combined with psychological-behavioral modification therapy improved the behavioral problems of ADHD children, enhanced their cognitive function, and reduced the adverse reactions to drug treatment.展开更多
The quenching interaction of atomoxetine(ATX) with bovine serum albumin(BSA) was studied in vitro under optimal physiological condition(pH=7.4) by multi-spectroscopic techniques. The mechanism of ATX-BSA system was a ...The quenching interaction of atomoxetine(ATX) with bovine serum albumin(BSA) was studied in vitro under optimal physiological condition(pH=7.4) by multi-spectroscopic techniques. The mechanism of ATX-BSA system was a dynamic quenching process and was confirmed by the fluorescence spectra and lifetime measurements. The number of binding sites, binding constants and other binding characteristics were computed. Thermodynamic parameters ΔH^0 and ΔS^0 indicated that intermolecular hydrophobic forces predominantly stabilized the drug-protein system. The average binding distance between BSA and ATX was studied by F?rsters theory. UV-absorption, Fourier transform infrared spectroscopy(FT-IR), circular dichroism(CD), synchronous spectra and three-dimensional(3D) fluorescence spectral results revealed the changes in micro-environment of secondary structure of protein upon the interaction with ATX. Displacement of site probes and the effects of some common metal ions on the binding of ATX with BSA interaction were also studied.展开更多
The bitterness of a drug is a major challenge for patient acceptability and compliance,especially for children.Due to the toxicity of medication,a human taste panel test has certain limitations.Atomoxetine hydrochlori...The bitterness of a drug is a major challenge for patient acceptability and compliance,especially for children.Due to the toxicity of medication,a human taste panel test has certain limitations.Atomoxetine hydrochloride(HCl),which is used for the treatment of attention deficit/hyperactivity disorder(ADHD),has an extremely bitter taste.The aim of this work is to quantitatively predict the bitterness of atomoxetine HCl by a biosensor system.Based on the mechanism of detection of the electronic tongue(Etongue),the bitterness of atomoxetine HCl was evaluated,and it was found that its bitterness was similar to that of quinine HCl.The bitterness threshold of atomoxetine HCl was 8.61μg/ml based on the Change of membrane Potential caused by Adsorption(CPA)value of the BT0 sensor.In this study,the taste-masking efficiency of 2-hydroxypropyl-β-cyclodextrin(HP-β-CyD)was assessed by Euclidean distances on a principle component analysis(PCA)map with the SA402B Taste Sensing System,and the host–guest interactions were investigated by differential scanning calorimetry(DSC),powder X-ray diffraction(XRD),nuclear magnetic resonance(NMR)spectroscopy and scanning electron microscopy(SEM).Biosensor evaluation and characterization of the inclusion complex indicated that atomoxetine HCl could actively react with 2-hydroxypropyl-β-cyclodextrin.展开更多
Treatment of attention deficit hyperactivity disorder with medications is helpful in less than 60% of cases suggesting the necessity of development of novel drugs. The most accepted animal model of the disease is outb...Treatment of attention deficit hyperactivity disorder with medications is helpful in less than 60% of cases suggesting the necessity of development of novel drugs. The most accepted animal model of the disease is outbred spontaneously hypertensive rat strain. It was recently found in a novel enrichment discrimination test that the rat strain includes attentionally-low and -high phenotypes and clinically efficient drug for the treatment of the disorder atomoxetine is capable of ameliorating the enrichment discrimination by the attentionally-low rats. The present study aimed to test the generality of these findings in outbred CD-1 mice assessed in the same experimental design. The frequency distribution of the enrichment discrimination ratio differed from the curve expected under the normality hypothesis and had a bimodal shape suggesting the existence of attentionally-low and -high mouse phenotypes. Atomoxetine (3 mg/kg, orally, once daily for 4 days) selectively enhanced enrichment discrimination in mice of attentionally-low phenotype only. The present results generalize and extend findings previously reported in spontaneously hypertensive rats and suggest that the present model could be useful in studies of the neurobiological mechanisms of attention deficiency in rodents and for screening of novel drug candidates for treatment of attention deficit disorder.展开更多
Background:Freezing of gait(FoG)is a common and debilitating condition in Parkinson’s disease(PD)associated with executive dysfunction.A subtype of FoG does not respond to dopaminergic therapy and may be related to n...Background:Freezing of gait(FoG)is a common and debilitating condition in Parkinson’s disease(PD)associated with executive dysfunction.A subtype of FoG does not respond to dopaminergic therapy and may be related to noradrenergic deficiency.This pilot study explores the effects of atomoxetine on gait in PD patients with dopaunresponsive FoG using a novel paradigm for objective gait assessment.Findings:Ten patients with PD and dopa-unresponsive FoG were enrolled in this eight-week open label pilot study.Assessments included an exploratory gait analysis protocol that quantified spatiotemporal parameters during straight-away walking and turning,while performing a dual task.Clinical,and subjective assessments of gait,quality of life,and safety were also administered.The primary outcome was a validated subjective assessment for FoG(FOG-Q).Atomoxetine was well tolerated,however,no significant change was observed in the primary outcome.The gait analysis protocol correlated well with clinical scales,but not with subjective assessments.DBS patients were more likely to increase gait velocity(p=0.033),and improved in other clinical assessments.Conclusions:Objective gait analysis protocols assessing gait while dual tasking are feasible and useful for this patient population,and may be superior correlates of FoG severity than subjective measures.These findings can inform future trials in this population.展开更多
Aims: To investigate rates of attention-deficit hyperactivity disorder (ADHD) in patients with chronic pain attending a pain clinic, the effects of a screening measure for ADHD in patients with chronic pain, and the e...Aims: To investigate rates of attention-deficit hyperactivity disorder (ADHD) in patients with chronic pain attending a pain clinic, the effects of a screening measure for ADHD in patients with chronic pain, and the effects of ADHD drugs on both pain and ADHD symptoms. Methods: We retrospectively surveyed 110 patients with chronic pain visiting the Anesthesiology and Pain Relief Center at the University of Tokyo in Japan, who had also consulted a psychiatrist, between April 2012 and July 2015. Results: Of the total of 110 patients with chronic pain, 35 (31.8%) were also diagnosed with ADHD, and the average Wender Utah Rating Scale (WURS) score among the ADHD patients was 39.0 ± 22.1 (n = 25). Only 36.0% of these patients exceeded the cutoff value, suggesting that 64.0% of the patients with ADHD were not identified by screening with the WURS. Twenty-six patients initiated treatment with ADHD medication, with dosage adjustment completed in 21. Of these 21 patients 20 (95.0%) had improved ADHD symptoms. Improved pain symptoms were observed in 14 patients (66.6%), with a reduction in the pain numerical rating scale of 64.7% ± 30.1%. Conclusions: This is the first study investigating the comorbidity of ADHD and chronic pain at pain clinics showing a high level of comorbidity and amelioration of pain and ADHD symptoms with treatment. Careful interpretation is required when the WURS is used to screen patients with chronic pain.展开更多
Objectives: 1) To reveal, among spontaneously hypertensive rats, subpopulations that diverge in attention to objects enriching an empty cross-maze;2) To evaluate effect of clinically efficient drug for treatment of at...Objectives: 1) To reveal, among spontaneously hypertensive rats, subpopulations that diverge in attention to objects enriching an empty cross-maze;2) To evaluate effect of clinically efficient drug for treatment of attention deficiency atomoxetine on the attention to environmental cues in attentionally-low rats. Method: A novel paradigm that provides measure of attention towards enriching objects independent of general locomotor activity and spatial orientation is employed. The apparatus consists of 4-arm radial maze, two arms of which contain objects (enriched compartments). Animals exploring the objects typically stay longer in enriched parts of maze than in empty arms and have a higher score of enrichment discrimination ratio. Results: Frequency distribution of the enrichment discrimination ratio had clear bimodal shape that differed significantly from normal distribution suggesting the existence of subpopulations of attentionally-low and -high individuals. The attentionally-low phenotype did not show inferiority in spatial orientation as compared with attentionally-high phenotype. The phenotypes did not differ from each other in measures of locomo- tor activity and blood pressure. Atomoxetine (3 mg/kg, orally, once daily for 4 days) enhanced enrichment discrimina- tion in animals of attentionally-low phenotype. Single administration of the drug was ineffective. Conclusion: Popula- tion of spontaneously hypertensive rat includes two phenotypes of attentionally-low and -high individuals. Subchronic atomoxetine ameliorates attention to environmental cues in attentionally-low rats. The enrichment discrimination test could be useful in studies of neurobiology of attention deficit condition and for screening of novel drug candidates.展开更多
文摘Objective: To evaluate the therapeutic efficacy of atomoxetine hydrochloride (ATX) combined with psychological-behavioral modification therapy for attention-deficit/hyperactivity disorder (ADHD) in children. Methods: A total of 60 cases of ADHD children admitted to our hospital between November 2021 and November 2022 were selected and randomly grouped into Group I and Group II. There were 30 cases in Group I who were treated with ATX combined with psychological-behavioral modification therapy. There were 30 cases in Group II who were treated with ATX monotherapy, and the therapeutic effects were compared. Results: Before treatment, there was no difference in the behavioral problem scores and cognitive function indexes of the two groups (P>0.05). After treatment, the behavioral problem scores of Group I were lower than those of Group II, and the cognitive function indicators of Group I were lower than those of Group II (P < 0.05). The adverse reaction rate of Group I was lower than that of Group II, and the total effective rate was higher than that of Group II (P < 0.05). Conclusion: ATX combined with psychological-behavioral modification therapy improved the behavioral problems of ADHD children, enhanced their cognitive function, and reduced the adverse reactions to drug treatment.
基金Karnatak University, Dharwad, India, for providing UGC-UPE fellowshipUGC, New Delhi for the award of BSR Faculty Fellowship (F No.18-1/2011) to Prof. S.T. Nandibewoor
文摘The quenching interaction of atomoxetine(ATX) with bovine serum albumin(BSA) was studied in vitro under optimal physiological condition(pH=7.4) by multi-spectroscopic techniques. The mechanism of ATX-BSA system was a dynamic quenching process and was confirmed by the fluorescence spectra and lifetime measurements. The number of binding sites, binding constants and other binding characteristics were computed. Thermodynamic parameters ΔH^0 and ΔS^0 indicated that intermolecular hydrophobic forces predominantly stabilized the drug-protein system. The average binding distance between BSA and ATX was studied by F?rsters theory. UV-absorption, Fourier transform infrared spectroscopy(FT-IR), circular dichroism(CD), synchronous spectra and three-dimensional(3D) fluorescence spectral results revealed the changes in micro-environment of secondary structure of protein upon the interaction with ATX. Displacement of site probes and the effects of some common metal ions on the binding of ATX with BSA interaction were also studied.
基金Support received from the National Major Scientific and Technological Special Project for“Significant New Drugs Development”during the Thirteenth Five-year Plan Period,P.R.China(2018ZX09721003-002-004)the Major Research Project of Shandong Province,P.R.China(2018GSF118004)the Key Research and Development Program of Shandong Province,P.R.China(2018CXGC1411)for their support and encouragement in carrying out this work.
文摘The bitterness of a drug is a major challenge for patient acceptability and compliance,especially for children.Due to the toxicity of medication,a human taste panel test has certain limitations.Atomoxetine hydrochloride(HCl),which is used for the treatment of attention deficit/hyperactivity disorder(ADHD),has an extremely bitter taste.The aim of this work is to quantitatively predict the bitterness of atomoxetine HCl by a biosensor system.Based on the mechanism of detection of the electronic tongue(Etongue),the bitterness of atomoxetine HCl was evaluated,and it was found that its bitterness was similar to that of quinine HCl.The bitterness threshold of atomoxetine HCl was 8.61μg/ml based on the Change of membrane Potential caused by Adsorption(CPA)value of the BT0 sensor.In this study,the taste-masking efficiency of 2-hydroxypropyl-β-cyclodextrin(HP-β-CyD)was assessed by Euclidean distances on a principle component analysis(PCA)map with the SA402B Taste Sensing System,and the host–guest interactions were investigated by differential scanning calorimetry(DSC),powder X-ray diffraction(XRD),nuclear magnetic resonance(NMR)spectroscopy and scanning electron microscopy(SEM).Biosensor evaluation and characterization of the inclusion complex indicated that atomoxetine HCl could actively react with 2-hydroxypropyl-β-cyclodextrin.
文摘Treatment of attention deficit hyperactivity disorder with medications is helpful in less than 60% of cases suggesting the necessity of development of novel drugs. The most accepted animal model of the disease is outbred spontaneously hypertensive rat strain. It was recently found in a novel enrichment discrimination test that the rat strain includes attentionally-low and -high phenotypes and clinically efficient drug for the treatment of the disorder atomoxetine is capable of ameliorating the enrichment discrimination by the attentionally-low rats. The present study aimed to test the generality of these findings in outbred CD-1 mice assessed in the same experimental design. The frequency distribution of the enrichment discrimination ratio differed from the curve expected under the normality hypothesis and had a bimodal shape suggesting the existence of attentionally-low and -high mouse phenotypes. Atomoxetine (3 mg/kg, orally, once daily for 4 days) selectively enhanced enrichment discrimination in mice of attentionally-low phenotype only. The present results generalize and extend findings previously reported in spontaneously hypertensive rats and suggest that the present model could be useful in studies of the neurobiological mechanisms of attention deficiency in rodents and for screening of novel drug candidates for treatment of attention deficit disorder.
基金by the Barmore Fund for Parkinson’s Researchthe MUSC Department of Neurology and Neurosurgery,by the South Carolina Clinical&Translational Research(SCTR)Institute,with an academic home at the Medical University of South Carolina+1 种基金supported by NIH/NCATS Grant Number UL1TR000062by NIH NINDS Grant Number 1K23NS091391-01A1.
文摘Background:Freezing of gait(FoG)is a common and debilitating condition in Parkinson’s disease(PD)associated with executive dysfunction.A subtype of FoG does not respond to dopaminergic therapy and may be related to noradrenergic deficiency.This pilot study explores the effects of atomoxetine on gait in PD patients with dopaunresponsive FoG using a novel paradigm for objective gait assessment.Findings:Ten patients with PD and dopa-unresponsive FoG were enrolled in this eight-week open label pilot study.Assessments included an exploratory gait analysis protocol that quantified spatiotemporal parameters during straight-away walking and turning,while performing a dual task.Clinical,and subjective assessments of gait,quality of life,and safety were also administered.The primary outcome was a validated subjective assessment for FoG(FOG-Q).Atomoxetine was well tolerated,however,no significant change was observed in the primary outcome.The gait analysis protocol correlated well with clinical scales,but not with subjective assessments.DBS patients were more likely to increase gait velocity(p=0.033),and improved in other clinical assessments.Conclusions:Objective gait analysis protocols assessing gait while dual tasking are feasible and useful for this patient population,and may be superior correlates of FoG severity than subjective measures.These findings can inform future trials in this population.
文摘Aims: To investigate rates of attention-deficit hyperactivity disorder (ADHD) in patients with chronic pain attending a pain clinic, the effects of a screening measure for ADHD in patients with chronic pain, and the effects of ADHD drugs on both pain and ADHD symptoms. Methods: We retrospectively surveyed 110 patients with chronic pain visiting the Anesthesiology and Pain Relief Center at the University of Tokyo in Japan, who had also consulted a psychiatrist, between April 2012 and July 2015. Results: Of the total of 110 patients with chronic pain, 35 (31.8%) were also diagnosed with ADHD, and the average Wender Utah Rating Scale (WURS) score among the ADHD patients was 39.0 ± 22.1 (n = 25). Only 36.0% of these patients exceeded the cutoff value, suggesting that 64.0% of the patients with ADHD were not identified by screening with the WURS. Twenty-six patients initiated treatment with ADHD medication, with dosage adjustment completed in 21. Of these 21 patients 20 (95.0%) had improved ADHD symptoms. Improved pain symptoms were observed in 14 patients (66.6%), with a reduction in the pain numerical rating scale of 64.7% ± 30.1%. Conclusions: This is the first study investigating the comorbidity of ADHD and chronic pain at pain clinics showing a high level of comorbidity and amelioration of pain and ADHD symptoms with treatment. Careful interpretation is required when the WURS is used to screen patients with chronic pain.
文摘Objectives: 1) To reveal, among spontaneously hypertensive rats, subpopulations that diverge in attention to objects enriching an empty cross-maze;2) To evaluate effect of clinically efficient drug for treatment of attention deficiency atomoxetine on the attention to environmental cues in attentionally-low rats. Method: A novel paradigm that provides measure of attention towards enriching objects independent of general locomotor activity and spatial orientation is employed. The apparatus consists of 4-arm radial maze, two arms of which contain objects (enriched compartments). Animals exploring the objects typically stay longer in enriched parts of maze than in empty arms and have a higher score of enrichment discrimination ratio. Results: Frequency distribution of the enrichment discrimination ratio had clear bimodal shape that differed significantly from normal distribution suggesting the existence of subpopulations of attentionally-low and -high individuals. The attentionally-low phenotype did not show inferiority in spatial orientation as compared with attentionally-high phenotype. The phenotypes did not differ from each other in measures of locomo- tor activity and blood pressure. Atomoxetine (3 mg/kg, orally, once daily for 4 days) enhanced enrichment discrimina- tion in animals of attentionally-low phenotype. Single administration of the drug was ineffective. Conclusion: Popula- tion of spontaneously hypertensive rat includes two phenotypes of attentionally-low and -high individuals. Subchronic atomoxetine ameliorates attention to environmental cues in attentionally-low rats. The enrichment discrimination test could be useful in studies of neurobiology of attention deficit condition and for screening of novel drug candidates.
