Investigation of serum and brain superoxide dismutase levels depending on atomoxetine used in attention-deficit/hyperactivity disorder treatment: A combination of in vivo and molecular docking studies.

This study aims to determine whether atomoxetine (ATX), used as an alternative to methylphenidate, affects superoxide dismutase (SOD) activity besides glutathione (GSH) and malondialdehyde (MDA) levels, apart from determining possible effects of ATX on SOD activity through molecular docking studies. 24 male Wistar rats were divided into 4 groups, each containing 6 members. After a 6-week application of ATX, blood samples and brain tissues were obtained from the rats for biochemical analyses. Besides, molecular docking studies were conducted using PyRx and Discovery Studio 3.0 programs. No significant difference occurred in GSH and MDA levels after ATX application. A high-dose application of ATX caused a statistically significant change only in the serum-SOD activity compared to that of Control Group. Molecular docking studies revealed that ATX settled in the biggest space rather than the catalytic regions of Cu2Zn2-SOD. Our biochemical and molecular docking data showed that ATX, an alternative drug to stimulant methylphenidate, showed no significant changes in the antioxidant defence system at either low or therapeutic doses after long-term use. Therefore, we suggest ATX could be used as a substitute for methylphenidate in the long-term treatment of ADHD.

Taste masking of water-soluble drug by solid lipid microspheres: a child-friendly system established by reversed lipid-based nanoparticle technique.

OBJECTIVES: A child-friendly taste-masking strategy using solid lipid microsphere (SLM) has been proposed to obscure the undesirable taste of some water-soluble drugs. In this study, the reversed lipid-based nanoparticle (RLBN) technique was used to encapsulate a water-soluble drug to facilitate the preparation of SLM. METHODS: The model drug used was atomoxetine hydrochloride (ATX), and a three-step method was used to prepare ATX-RLBN. Taste-masking microsphere (ATX-RLBN-SLM) was prepared by the spray chilling method. The drug release mechanism was studied by high-performance liquid chromatography and scanning electron microscopy. Moreover, in vitro taste evaluation method was established and ATX bioavailability was investigated employing pharmacokinetic studies. KEY FINDINGS: The obtained ATX-RLBN-SLM had smooth spherical particles with a size of about 80 µm. The drug encapsulation and loading efficiencies were 98.28% ± 0.59% and 0.89% ± 0.04%, respectively. In vitro drug release studies showed that nearly 96% drug was retained in the microspheres within 10 min at pH 6.8 and a complete release was triggered by lipase, accompanied by variation in the morphology. Taste assessment revealed that ATX-RLBN-SLM could efficiently mask the bitter taste and improved the bioavailability of ATX. CONCLUSIONS: Atomoxetine hydrochloride-reversed lipid-based nanoparticle-solid lipid microsphere exhibited excellent taste-masking effect with negligible leakage in the oral cavity environment and thorough collapse upon lipase stimulation, simultaneously enhancing the bioavailability of ATX. The study paves a new way to efficiently mask the undesirable taste of some water-soluble drugs.

The Treatment of Primary Orthostatic Hypotension.

OBJECTIVE: To review the efficacy and safety of pharmacological and nonpharmacological strategies used to treat primary orthostatic hypotension (OH). DATA SOURCES: A literature review using PubMed and MEDLINE databases searching hypotension, non-pharmacological therapy, midodrine, droxidopa, pyridostigmine, fludrocortisone, atomoxetine, pseudoephedrine, and octreotide was performed. STUDY SELECTION AND DATA EXTRACTION: Randomized or observational studies, cohorts, case series, or case reports written in English between January 1970 and November 2016 that assessed primary OH treatment in adult patients were evaluated. DATA SYNTHESIS: Based on the chosen criteria, it was found that OH patients make up approximately 15% of all syncope patients, predominantly as a result of cardiovascular or neurological insults, or offending medication. Nonpharmacological strategies are the primary treatment, such as discontinuing offending medications, switching medication administration to bedtime, avoiding large carbohydrate-rich meals, limiting alcohol, maintaining adequate hydration, adding salt to diet, and so on. If these fail, pharmacotherapy can help ameliorate symptoms, including midodrine, droxidopa, fludrocortisone, pyridostigmine, atomoxetine, sympathomimetic agents, and octreotide. CONCLUSIONS: Midodrine and droxidopa possess the most evidence with respect to increasing blood pressure and alleviating symptoms. Pyridostigmine and fludrocortisone can be used in patients who fail to respond to these agents. Emerging evidence with low-dose atomoxetine is promising, especially in those with central autonomic failure, and may prove to be a viable alternative treatment option. Data surrounding other therapies such as sympathomimetic agents or octreotide are minimal. Medication management of primary OH should be guided by patient-specific factors, such as tolerability, adverse effects, and drug-drug and drug-disease interactions.

The effects of atomoxetine on emotional control in adults with ADHD: An integrated analysis of multicenter studies.

PURPOSE: To investigate the effects of atomoxetine on emotional control in adults with ADHD. METHODS: We performed an integrated analysis using individual patient data pooled from three Eli Lilly-sponsored studies. An integrated analysis can be viewed as a meta-analysis of individual patient-level data, rather than study-level summary data. RESULTS: Two populations were identified: a large sample of patients with pre-treatment baseline data (the "overall population"; n=2846); and a subset of these patients with placebo-controlled efficacy data from baseline to 10 or 12 weeks after initiating treatment (the "placebo-controlled population"; n=829). At baseline, in the overall population, ∼50% of ADHD patients had BRIEF-AS (Behavior Rating Inventory of Executive Function-Adult Version Self-Report) Emotional control subscores between 21 and 30, compared with ∼10% of normative subjects in the BRIEF-A manual. At endpoint, in the placebo-controlled population, atomoxetine led to a small (effect size 0.19) but significant (P=0.013) treatment effect for emotional control. The effect size was 0.32 in patients with BRIEF-AS Emotional control scores>20 at baseline. Improvements in emotional control correlated with improvements in the core ADHD symptoms and quality-of-life. DISCUSSION: As deficient emotional control is associated with impaired social, educational and occupational functioning over and above that explained by core ADHD symptoms alone, improvements in emotional control may be clinically relevant. CONCLUSION: At baseline, adults with ADHD were more likely to have impaired emotional control than normative subjects. In the adult ADHD patients, atomoxetine treatment was associated with improvements in emotional control, as well as in core ADHD symptoms and quality-of-life.