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The current study aimed to evaluate the efficacy of orally administered rapid mini-tablets containing atomoxetine hydrochloride (ODMT) relative to the conventional capsule formulation of atomoxetine hydrochloride (ATO). To mask the bitter taste of ATO and render it more palatable for pediatric administration in individuals with Attention Deficit Hyperactivity Disorder (ADHD), an inclusion complex of ATO with β-cyclodextrin (β-CD) was synthesized. The ODMT and conventional capsule ATO formulations were administered orally to a cohort of ADHD rat pups born to nicotine-exposed dams, facilitating an in vivo efficacy assessment. Behavioral assays, including the open field test, novel object recognition test, and Barnes maze test, were conducted pre- and post-administration of the therapeutics. The outcomes suggested that the ODMT formulation, incorporating ATO-β-CD inclusion complexes, shows promise as a viable alternative to the capsule form of ATO. Conclusively, the preparation of the ATO-β-CD complexes and ODMTs leveraged a factorial experimental design, with the animal model being subjected to nicotine-induced hyperactivity to provide a unique evaluative framework for the ODMT formulation under development. [ABSTRACT FROM AUTHOR]

The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension–related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI. [ABSTRACT FROM AUTHOR]

In recent years, exposure to triclosan (TCS) has been linked to an increase in psychiatric disorders. Nonetheless, the precise mechanisms of this occurrence remain elusive. Therefore, this study developed a long-life TCS-exposed rat model, an SH-SY5Y cell model, and an atomoxetine hydrochloride (ATX) treatment model to explore and validate the neurobehavioral mechanisms of TCS from multiple perspectives. In the long-life TCS-exposed model, pregnant rats received either 0 mg/kg (control) or 50 mg/kg TCS by oral gavage throughout pregnancy, lactation, and weaning of their offspring (up to 8 weeks old). In the ATX treatment model, weanling rats received daily injections of either 0 mg/kg (control) or 3 mg/kg ATX via intraperitoneal injection until they reached 8 weeks old. Unlike the TCS model, ATX exposure only occurred after the pups were weaned. The results indicated that long-life TCS exposure led to attention-deficit hyperactivity disorder (ADHD)-like behaviors in male offspring rats accompanied by dopamine-related mRNA and protein expression imbalances in the prefrontal cortex (PFC). Moreover, in vitro experiments also confirmed these findings. Mechanistically, TCS reduced dopamine (DA) synthesis, release, and transmission, and increased reuptake in PFC, thereby reducing synaptic gap DA levels and causing dopaminergic deficits. Additional experiments revealed that increased DA concentration in PFC by ATX effectively alleviated TCS-induced ADHD-like behavior in male offspring rats. These findings suggest that long-life TCS exposure causes ADHD-like behavior in male offspring rats through dopaminergic deficits. Furthermore, ATX treatment not only reduce symptoms in the rats, but also reveals valuable insights into the neurotoxic mechanisms induced by TCS.

A cost-effective and innovative reverse phase high performance liquid chromatography (RPHPLC) technique has been devised to accurately and precisely measure the quantity of Atomoxetine Hydrochloride in both large quantities and solid dosage forms. The separation process was conducted using an Xterra RP 18 column with dimensions of 250 mm × 4.6 mm and a particle size of 5 μ. The experiment used the isocratic technique, with a mobile phase consisting of a 70:30 (v/v) mixture of water and methanol. The mobile phase was injected into the column using a pump, with a flow rate of 1.0 mL min-1. The eluent from the column was detected using a UV detector set to operate at a wavelength of 280 nm. The experiment had a duration of 5 minutes, during which the column was consistently kept at the ambient temperature. The determined retention time for Atomoxetine Hydrochloride was 3.08 minutes. The standard curves exhibited a linear relationship throughout the concentration range of 02-10 μg/ml, with a high coefficient of determination (R2 = 0.9997). The study resulted in a variety of percentage recoveries, ranging from 99% to 101%. Moreover, the Relative Standard Deviation (RSD) was computed to be 0.290%. The measured percentage composition of a commercially available formulation of Atomoxetine Hydrochloride was determined to be 100.18%. The approach was verified in accordance with the requirements set out by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The suggested RP-HPLC technique has been validated via research, showcasing its characteristics of simplicity, specificity, speed, reliability, and uniformity. Therefore, the approach suggested in this study may be used for the regular analysis of Atomoxetine Hydrochloride in both its concentrated and solid states, specifically with the aim of assuring quality control. [ABSTRACT FROM AUTHOR]

Objectives: A simple, sensitive, selective, and cost-effective colorimetric method has been established for the quantitative estimation of atomoxetine hydrochloride in bulk and formulation. Materials and Methods: It was established based on the visible reaction between atomoxetine hydrochloride and 1,2-naphthoquinone-4-sulfonic acid sodium salt in a basic medium (potassium hydroxide). The resulting orange colored chromogen exhibited an absorption maximum at 474 nm. Results: Based on the optimization studies, distilled water as the solvent, 1% w/v potassium hydroxide (2 mL), and 0.3% w/v 1,2-naphthoquinone-4-sulfonic acid sodium salt (2 mL) were used in the method. The developed method was validated per the International Council for Harmonization (ICH) guidelines. The linearity was found at a concentration of 10-50 µg/mL. The method showed a good correlation between the concentration of atomoxetine hydrochloride and its absorbance. The correlation coefficient (r2) of 0.999 evidenced the same. The limits of detection and quantification were 0.20 and 0.606 µg/mL, respectively, for atomoxetine hydrochloride. The accuracy and precision of the method were also evaluated and the results obtained were within the acceptance criteria (relative standard deviation % < 2.00). The percentage assay of atomoxetine hydrochloride proved to be 101.52, which is in accordance with its label claim. Conclusion: The developed method is non-complex and can be effectively employed in the analytical practices of atomoxetine hydrochloride in pharmaceutical dosage forms. [ABSTRACT FROM AUTHOR]

Background: Recent research shows that most of the patients with multiple sclerosis (MS) have cognitive-like disorders. Due to the beneficial effects of atomoxetine on improving cognition in limited animal and human surveys, the aim of the present study was to investigate the effect of the atomoxetine on improving cognitive disorders of MS. Methods: This study was a parallel, randomized clinical trial, designed to investigate the effect of atomoxetine drug on the improvement of cognitive impairment (CI) in MS, from April 2021 to March 2022. According to the inclusion and exclusion criteria, a total of 52 participants were involved in the study and then randomly divided in two groups of 26. Experimental group was treated with atomoxetine and the control group was treated with placebo. The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) test was performed for assessment at the beginning and after 3 months. The California Verbal Learning Test (CVLT), the CVLT-delay, the Brief Visuospatial Memory Test-Revised (BVMT-R), and the Symbol Digit Modalities Test (SDMT) were used to evaluate the CI and changes following medication. Finally, data were analyzed by SPSS software at significance level of 0.05. Results: The mean age of patients in the experimental group was 37.7 ± 8.5 and in the placebo group was 37.8 ± 7.6 (P = 0.32). The results showed significant changes in cognitive levels before and after the use of atomoxetine and also in comparison to the placebo group (P < 0.05). Conclusion: This study showed that atomoxetine improved the cognitive domains after administration compared to placebo. [ABSTRACT FROM AUTHOR]

Abstract Aim Atomoxetine (ATX) is a non‐central stimulant and a standard treatment for adult attention‐deficit/hyperactivity disorder (ADHD). The long‐term efficacy of Atomoxetine is about 40% at 6 months. The variability in efficacy between individuals is thought to be related to patient‐specific factors, but no detailed research has been conducted. In this retrospective cohort study, we aimed to identify the factors associated with Atomoxetine efficacy. Methods A total of 147 patients with attention‐deficit/hyperactivity disorder aged ≥18 years who were using Atomoxetine for the first time were included in this study. The outcome was treatment success (treatment maintained for at least 6 months and improvement in symptoms). Symptom assessment was based on the overall improvement in symptoms judged by an expert physician. Results Of the patient sample, 103 (70.1%) achieved the outcome. Logistic regression analysis identified “the maximum dose of ATX” and “gambling habit” as factors associated with efficacy ( P

Attention deficit hyperactivity disorder is not only a childhood disorder, but a disorder of childhood-onset. Attention deficit hyperactivity disorder, first described as attention deficit, encompasses a larger spectrum of symptoms that appear not only in children, but also in adults, even in those over 65 years of age. Evaluation of this symptom spectrum is important, as affected adults, especially females, are likely overlooked or misdiagnosed in childhood. They may present later with dire outcomes, such as academic failure, problematic parenting behaviours, workplace problems, risky sexual behaviour leading to miscarriages or sexually transmitted infections, and increased suicide rates due to their vulnerability to depression and anxiety-related symptoms. Structural and biochemical findings were associated with this disorder. Additionally, there are many neuropathological models proposed to explain the nature of attention deficit hyperactivity disorder, such as those proposed by Sergeant and Barkley. Although a lot is known about attention deficit hyperactivity disorder so far, there is still a large lack of information about its prognosis and prevalence in vulnerable or minority populations. In this review, we aim to provide an overview of not only the pathophysiology, but the spectrum of attention deficit hyperactivity disorder symptoms throughout the lifespan with an emphasis on the childhood-onset nature of this disorder. [ABSTRACT FROM AUTHOR]