Antipsychotic Drugs Olanzapine Research Articles

B-303 Stability of Antipsychotic Drugs in Patient Serum and Plasma Clinical Samples

Abstract Background Therapeutic drug monitoring (TDM) of antipsychotic blood levels is strongly recommended (clozapine and olanzapine) and recommended (risperidone, aripiprazole, and quetiapine) by ASCP/AGNP Consensus Statement. For effective TDM, it is paramount to understand both the stability of the antipsychotic drugs in serum and plasma, as well as any differences in levels due to sample matrix to ensure robust concentration determinations. While clozapine levels are considered equivalent in serum and plasma, we included in our study four additional antipsychotics. Methods Whole blood samples from ten patients taking clozapine, risperidone, aripiprazole, olanzapine, or quetiapine were collected in one red top tube and in one purple top tube according to an IRB-approved protocol. Samples were then processed within 2 hours of collection to obtain matched serum and K2EDTA plasma samples from each of the patients. CE marked immunoassays for the measurement of clozapine (also FDA cleared), total risperidone/paliperidone, total aripiprazole, olanzapine, and quetiapine were used to quantitate drug concentrations. Stability of the samples was assessed at 4°C, ambient room temperature (ART), and frozen at -80°C, with respect to their Day 0 concentration by measurement of six replicates at each timepoint using the immunoassays. Results Comparison of Day 0 values between serum and plasma for the same patient showed ±9% bias between sample matrices for all drugs, except olanzapine which showed differences up to ±15%. Average bias between serum and plasma was ≤-5% (olanzapine: -9%). All drugs were stable (±15% deviation from Day 0; olanzapine up to ±23%) in serum and in plasma for 7 days at both 4°C and ART and for up to 8 months frozen. Conclusions This study demonstrated that (1) the antipsychotic drugs clozapine, risperidone, aripiprazole, olanzapine, and quetiapine have sufficient stability in both serum and plasma for effective TDM and (2) for TDM, serum or plasma may be used.

The crystal structure of olanzapine form III.

The antipsychotic drug olanzapine is well known for its complex polymorphism. Although widely investigated, the crystal structure of one of its anhydrous polymorphs, form III, is still unknown. Its appearance, always in concomitance with forms II and I, and the impossibility of isolating it from that mixture, have prevented its structure determination so far. The scenario has changed with the emerging field of 3D electron diffraction (3D ED) and its great advantages in the characterization of polyphasic mixtures of nanosized crystals. In this study, we show how the application of 3D ED allows the ab initio structure determination and dynamical refinement of this elusive crystal structure that remained unknown for more than 20 years. Olanzapine form III is monoclinic and shows a similar but shifted packing with respect to form II. It is remarkably different from the lowest-energy structures predicted by the energy-minimization algorithms of crystal structure prediction.

Gold nanoparticles assisted colorimetric sensing of paroxetine, duloxetine, and olanzapine in aqueous and micellar systems with improved sensitivity

The present study explored a rapid and facile colorimetric identification of two antidepressants (paroxetine and duloxetine) and one antipsychotic drug (olanzapine) in aqueous and micellar systems using citrate-stabilized gold nanoparticles (Cit-AuNPs). The sensing approach involved hydrogen bonding and electrostatic interactions on the surface of Cit-AuNPs. The attributes of Cit-AuNPs and their interactions with the drugs were probed using characterization techniques like UV–Vis spectroscopy, scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta potential measurement, and Fourier-transform infrared spectroscopy (FT-IR). Various factors including the volume of Cit-AuNPs, pH, reaction time, surfactant concentration, and the sequence of addition of reagents were optimized to inspect their impacts on sensing results. Under optimized conditions, the probe showed good linearity for the three drugs at the nanomolar (nM) range. Consequently, the color of the Cit-AuNP solution transformed from red to royal purple and blue, which was visible to the naked eye and monitored by visible absorption spectra. This label-free optical detection approach could recognize paroxetine (Prx), duloxetine (Dlx), and olanzapine (Olz) in aqueous system at concentrations ranging from 1 to 17 nM with a limit of detection (LOD) of 0.312, 0.258, and 0.418 nM (S/N = 3), respectively. Meanwhile, the sensitivity was improved in the Triton X-100 (TX-100) micellar system with LOD of 0.029, 0.030, and 0.029 nM for Prx, Dlx, and Olz, respectively accompanied by a shift in the absorption bands. The micellar system contributes stability to the Cit-AuNP-drug complex. The devised colorimetric approach was convenient and did not require any complex equipment. It was efficaciously used to detect three drugs in pharmaceutical products, spiked human urine, and blood serum samples with satisfactory recoveries of 99.83–103.45% and RSD < 3.5%. Notably, the sensing assay demonstrated good selectivity for three drugs in the existence of commonly encountered foreign species and certain common drugs with a relative error below 3%. The results of the present study were statistically compared with reference methodology. The results were validated with no significant difference between the devised and reported approaches considering precision and accuracy, respectively.

Facile surface modification of the poly(l-cysteine) on 2D-printed reduced graphene oxide electrode to fabricate a highly sensitive electrochemical sensor for determining the antipsychotic drug olanzapine

Amino acid-based polymers are alternative modifiers for electrode surface modification that can be simply and rapidly synthesized through electrochemical methods. Hence, we aim to develop a novel and easy-to-construct electrochemical sensor based on a two-dimensional-printed reduced graphene oxide electrode modified with poly(l-cysteine) for the determination of the antipsychotic drug olanzapine. The poly(l-cysteine) was employed as the only modifier for electrode surface modification, which was conducted via a single-step electropolymerization procedure. The surface composition and morphology of the developed sensor were examined by using a field emission scanning electron microscope, energy-dispersive X-ray spectroscopy, fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The electrochemical characterization of the sensor was also performed by utilizing cyclic voltammetric and electrochemical impedance spectroscopic techniques. All electrochemical parameters and analytical performances of interest were thoroughly investigated. Under optimal conditions, the developed approach showed broad linear dynamic ranges of 10–1000 and 1500–5000 nM and a low detection limit of 0.91 nM in the detection of trace amounts of olanzapine. When the proposed approach was used to analyze olanzapine in human serum samples to verify its feasibility, it exhibited high accuracy and good precision. In contrast to conventional electrodes, our newly developed electrochemical electrode could be an appropriate device for monitoring the effectiveness and safety of the antipsychotic drug olanzapine.

Protein Kinases in Obesity, and the Kinase-Targeted Therapy.

The action of protein kinases and protein phosphatases is essential for multiple physiological responses. Each protein kinase displays its own unique substrate specificity and a regulatory mechanism that may be modulated by association with other proteins. Protein kinases are classified as dual-specificity kinases and dual-specificity phosphatases. Dual-specificity phosphatases are important signal transduction enzymes that regulate various cellular processes in coordination with protein kinases and play an important role in obesity. Impairment of insulin signaling in obesity is largely mediated by the activation of the inhibitor of kappa B-kinase beta and the c-Jun N-terminal kinase (JNK). Oxidative stress and endoplasmic reticulum (ER) stress activate the JNK pathway which suppresses insulin biosynthesis. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are important for proper regulation of glucose metabolism in mammals at both the hormonal and cellular levels. Additionally, obesity-activated calcium/calmodulin dependent-protein kinase II/p38 suppresses insulin-induced protein kinase B phosphorylation by activating the ER stress effector, activating transcription factor-4. To alleviate lipotoxicity and insulin resistance, promising targets are pharmacologically inhibited. Nifedipine, calcium channel blocker, stimulates lipogenesis and adipogenesis by downregulating AMPK and upregulating mTOR, which thereby enhances lipid storage. Contrary to the nifedipine, metformin activates AMPK, increases fatty acid oxidation, suppresses fatty acid synthesis and deposition, and thus alleviates lipotoxicity. Obese adults with vascular endothelial dysfunction have greater endothelial cells activation of unfolded protein response stress sensors, RNA-dependent protein kinase-like ER eukaryotic initiation factor-2 alpha kinase (PERK), and activating transcription factor-6. The transcriptional regulation of adipogenesis in obesity is influenced by AGC (protein kinase A (PKA), PKG, PKC) family signaling kinases. Obesity may induce systemic oxidative stress and increase reactive oxygen species in adipocytes. An increase in intracellular oxidative stress can promote PKC-β activation. Activated PKC-β induces growth factor adapter Shc phosphorylation. Shc-generated peroxides reduce mitochondrial oxygen consumption and enhance triglyceride accumulation and lipotoxicity. Liraglutide attenuates mitochondrial dysfunction and reactive oxygen species generation. Co-treatment of antiobesity and antidiabetic herbal compound, berberine with antipsychotic drug olanzapine decreases the accumulation of triglyceride. While low-dose rapamycin, metformin, amlexanox, thiazolidinediones, and saroglitazar protect against insulin resistance, glucagon-like peptide-1 analog liraglutide inhibits palmitate-induced inflammation by suppressing mTOR complex 1 (mTORC1) activity and protects against lipotoxicity.

Drug therapy combined with PBL on depression of college students

BackgroundThe treatment of depression is mainly to eliminate and improve the symptoms of patients. At present, there are a variety of clinical antidepressants for the treatment of depression, however, there are still some patients with no significant therapeutic effect. When the effect of antidepressants alone is not satisfactory for patients with refractory depression, synergistic therapy can be considered, which is atypical antipsychotics being used as synergists in combination with antidepressants. Based on this background, this project conducted relevant research on patients with depression as research samples.Subjects and MethodsThe control group was given paroxetine tablets at a dose of 20 mg/d as prescribed by the doctor, and the dose was increased to 30 mg/d after 1 week. On the basis of the control group, the study group was given atypical antipsychotic olanzapine tablets at a dose of 5 mg/d as prescribed by the doctor. The score of depression degree was represented by the Hamilton Rating Scale for Depression (HAMD) score. The score of life quality was referred to the brief form of Health survey (SF-36 scale). SPSS20.0 software was used for statistical processing of various indicators of the 2 groups.ResultsAfter treatment, HAMD scores decreased and SF-36 scores increased in the study group and control group, and HAMD scores and SF-36 scores in the study group were significantly better than those in the control group after treatment (P &lt; 0.05).ConclusionsAntidepressant drugs (paroxetine tablets) combined with atypical antipsychotic drugs (olanzapine tablets) are effective in the treatment of depression, and can effectively improve the quality of life of patients.Acknowledgement2019 Teaching Reform Research Project of Chongqing Municipal Education Commission (No. 193144); Chongqing Educational Science Planning Project (No. 2019-GX-352).

Near-Infrared Fluorescent Probe for the In Situ Visualization of Oxidative Stress in the Brains of Neuroinflammatory and Schizophrenic Mice.

Schizophrenia is a common mental disorder with unclear mechanisms. Oxidative stress and neuroinflammation play important roles in the pathological process of schizophrenia. Superoxide anion (O2•-) is an important oxidative stress biomarker in vivo. However, due to the existence of the blood-brain barrier (BBB), few near-infrared (NIR) fluorescent probes have been used for the sensing and detection of O2•- in the brain. With this research, we developed the first near-infrared fluorescent probe (named CT-CF3) for noninvasive detection of endogenous O2•- in the brain of mice. Enabling fluorescence monitoring of the dynamic changes in O2•- flux due to the prolonged activation of microglia in neuroinflamed and schizophrenic (SZ) mice brains, thereby providing direct evidence for the relationship between oxidative stress, neuroinflammation, and schizophrenia. Furthermore, we confirmed the O2•- burst in the brains of first-episode schizophrenic mice and assessed the effect of two atypical antipsychotic drugs (risperidone and olanzapine) on redox homeostasis.

Study on binding affinity profile, bioactivity, and lipophilicity of selected antipsychotic drugs

Schizophrenia is a complex mental illness that affects almost 1% of the population and has no curative treatment. Currently, available neuroleptic drugs have severe limitations and induce drug-related adverse effects. Receptor binding affinity parameters and lipophilicity are important characteristics that describe the bioactivity of these drugs. Lipophilicity is an important physicochemical property of a drug, which predicts distribution, binding to plasma protein, crossing the blood–brain barrier, and biological activity. Five antipsychotic drugs (Haloperidol, Risperidone, Aripiprazole, Olanzapine, and Quetiapine) were selected and the experimental determination of lipophilicity was carried out by reverse phase thin-layer chromatography (RP-TLC) using four types of stationary phases (RP-18, CN, Diol, and NH2 modified silica gel HPTLC plates) and acetonitrile-water with increasing percentage of acetonitrile and 0.2% formic acid in each case as mobile phase. Lipophilicity parameters (mRM and RM0) calculated from the experimental chromatographic retention data were discussed in terms of the correlation with different receptor binding affinity parameters determined by computational methods.

Intranasal administration of olanzapine has beneficial outcome in a rat activity-based anorexia model

The atypical antipsychotic drug olanzapine is prescribed despite clinical studies on olanzapine treatment showing mixed results on treatment efficacy in anorexia nervosa. We investigated the effect of systemic and intranasal administration of olanzapine in the activity-based anorexia (ABA) model. Rats were habituated to a running wheel and exposed to the ABA model while treated with olanzapine. During ABA rats had 1.5 h of daily access to food and ad libitum access to a running wheel for seven consecutive days. Olanzapine was administered via an osmotic minipump (1, 2.75, and 7.5 mg/kg) or intranasally 2 h before dark onset (1 and 2.75 mg/kg). We monitored body weight, food intake, wheel revolutions, body temperature, and adipose tissue.We found 2.75 and 7.5 mg/kg systemic olanzapine decreased wheel revolutions during ABA. Relative adipose tissue mass was increased in the 7.5 mg/kg olanzapine-treated group while body weight, food intake, and body temperature were unaltered by the systemic olanzapine. 1 and 2.75 mg/kg intranasal olanzapine diminished wheel revolutions and body temperature during the first 2 h after administration. The intranasal olanzapine-treated rats had a higher body weight at the end of ABA.We find that olanzapine has beneficial outcomes in the ABA via two administration routes by acting mainly on running wheel activity. Intranasal olanzapine showed a rapid effect in the first hours after administration in reducing locomotor activity. We recommend further exploring intranasal administration of olanzapine in anorectic patients to assist them in coping with restlessness.

Eco-friendly synthesis of new olanzapine derivatives and evaluation of their anticancer potential.

New derivatives of the known antipsychotic drug olanzapine have been obtained as potential compounds with anticancer activity in two metabolically different breast cancer cell lines: MCF-7 and triple negative MDA-MB-231. The compounds were obtained under phase transfer catalysis (PTC) in the presence of microwave irradiation (MW) or ultrasound (")))"), evaluating the effect of solvents such as dimethylformamide, water, or choline chloride/urea (natural deep eutectic solvent, NaDES). In the best option, the compounds were obtained within 2 minutes with a yield of 57-86% in MW. Two of the obtained compounds which have a naphthalimide moiety and a pentyl (7) or hexyl chain (8) show pronounced cytotoxicity. Interestingly, neither olanzapine nor desmethylolanzapine (DOLA), which was one of the substrates for the synthesis reaction, showed any significant activity in the study.

Effects of the second-generation antipsychotic drugs aripiprazole and olanzapine on human adipocyte differentiation

Second-generation antipsychotics (SGAs), used as the cornerstone treatment for schizophrenia and other mental disorders, can cause adverse metabolic effects (e.g. obesity and type 2 diabetes). We investigated the effects of SGAs on adipocyte differentiation and metabolism. The presence of therapeutic concentrations of aripiprazole (ARI) or its active metabolite dehydroaripiprazole (DARI) during human adipocyte differentiation impaired adipocyte glucose uptake while the expression of gene markers of fatty acid oxidation were increased. Additionally, the use of a supra-therapeutic concentration of ARI inhibited adipocyte differentiation. Furthermore, olanzapine (OLA), a highly obesogenic SGA, directly increased leptin gene expression but did not affect adipocyte differentiation and metabolism. These molecular insights are novel, and suggest that ARI, but not OLA, may directly act via alterations in adipocyte differentiation and potentially by causing a switch from glucose to lipid utilization in human adipocytes. Additionally, SGAs may effect crosstalk with other organs, such as the brain, to exert their adverse metabolic effects.

Effects of Chronic Administration of Antipsychotic Drug (Olanzapine) on the Anterior Pituitary Gland of Adult Male Albino Rats and the Potential Protective Role of Hypericum Perforatum

Effects of Chronic Administration of Antipsychotic Drug (Olanzapine) on the Anterior Pituitary Gland of Adult Male Albino Rats and the Potential Protective Role of Hypericum Perforatum

The antipsychotic drug olanzapine altered lipid metabolism in the common carp (Cyprinus carpio L.): Insight from the gut microbiota-SCFAs-liver axis

Olanzapine (OLA) is a common drug used to treat schizophrenia and has recently come under increasing scrutiny as an emerging contaminant. However, its impact on lipid metabolism in fish and its mechanisms of action are not well understood. In this study, common carp were exposed to 0, 10, 100, and 250 μM OLA for 60 days. The results indicated that OLA exposure increased weight gain, total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG) and decreased high-density lipoprotein (HDL). In addition, lipids accumulated in the liver of the common carp. To explore the underlying mechanisms of action, gut microbiota, short-chain fatty acids (SCFAs), liver transcripts, and genes related to lipid metabolism were measured. It was discovered that OLA exposure altered the common carp gut microbiota composition and increased the abundance of SCFA-producing bacteria. Correspondingly, this study showed that OLA exposure increased the levels of SCFAs, which are highly relevant to the development of lipid accumulation. Transcriptome sequencing results indicated that OLA exposure could change lipid metabolism signalling pathways, including steroid biosynthesis, the PPAR signalling pathway, asglycerophospholipid metabolism, glycerolipid metabolism, and fatty acid metabolic pathways of the common carp. Additionally, OLA exposure interrupted lipid metabolism by means of significant upregulation of lipid synthesis-related genes, including pparγ, srebp1, and fas. OLA exposure also resulted in significant lipolysis-related gene downregulation, including cpt, lpl, hsl, and pparα. The results of this study indicated that contamination of aquatic environments with OLA alters lipid metabolism in common carp. In addition, the underlying mechanism might be due in part to the modulation of the gut microbiota-SCFA-PPAR signalling pathway.

Potentially Inappropriate Medication Among People With Dementia in China: A Nationwide Cross-Sectional Study.

Objectives: The purpose of this study was to explore the prevalence of potentially inappropriate medication (PIM) among older outpatients (age ≥ 65 years old) with dementia in eight cities in China using the AGS Beers criteria of 2019 and to identify the potential factor increasing the number of PIMs. Methods: A cross-sectional study about PIM in older outpatients with dementia from January 2020 to December 2020 was carried out in eight cities in China, Chengdu, Beijing, Guangzhou, Shanghai, Shenyang, Tianjin, Zhengzhou, and Hangzhou, distributing five major geographical regions in China (east, west, north, south, central). The diagnosis of dementia was based on the International Classification of Diseases (ICD-10) to identify. Based on the 2019 AGS Beers criteria, the PIM prescriptions were evaluated. The identification of potential factors was completed using a binary logistic regression model. Results: Of 18,624 older outpatients with dementia, 3.52% were detected with 1 PIM, and 35.91% received at least two PIMs. The antipsychotic drugs quetiapine and olanzapine were most frequently prescribed in patients with PIM, accounting for 8.01 and 7.36%, respectively. Logistic regression analyses showed that female patients with dementia aged >80 years who took more medications were exposed easily to PIM use. Conclusion: PIM use among older outpatients with dementia in China is highly prevalent, and the associated risk factors were increasing age, female sex, and number of medications. The most frequently prescribed drugs by clinicians were anpsychotropic drugs, which were much more frequent than other drugs.

Microbiological Investigation of the Effects of Olanzapine with Timokinon on the Intestine

The aim of our study is to examine the effect of thymoquinone (TQ) in obese rats induced with an antipsychotic drug olanzapine (OL). Thirty-five female Spraque-Dawley rats were divided into five groups (n = 7): Control, OL (2 mg / kg OL daily), OL + TQ1 (2 mg / kg OL + 20 mg / kg TQ), OL + TQ2 (2 mg / kg OL + 40 mg / kg TQ) and the OL + TQ3 group (2 mg / kg OL + 80 mg / kg TQ). On the 15th day of treatment, intestinal tissue was removed for analysis. It has been found that TQ treatment affects the levels of Firmicutes and Bacteroides at varying rates in the intestinal flora in OL + TQ1, OL + TQ2 and OL + TQ3 groups, and also has a significant role in the apoptotic effect of TQ. In conclusion, with this study, it was determined that the treatment of TQ has a protective property against the side effects of OL. TQ can be an effective treatment method to increase therapeutic effectiveness.

Synthesis, crystal structure, hirshfeld surface analysis, molecular docking and molecular dynamics studies of novel olanzapinium 2,5-dihydroxybenzoate as potential and active antipsychotic compound

The antipsychotic drug Olanzapine was crystallized with aromatic acid, 2,5-dihydroxybenzoic acid in isopropyl alcohol by slow evaporation which led to the formation of olanzapinium 2,5-dihydroxybenzoate crystalline salt. The structure of the compound was characterized by 1H-NMR, 13C-NMR, and single-crystal X-ray diffraction analysis. The Hirshfeld analyses were performed to quantify the order and nature of intermolecular interactions in the crystal network. Employing computational approaches, the compound was tested for its affinity against antipsychotic activity by molecular docking and molecular dynamic simulation to attest the conformational stability over time step of 100 ns. Besides, bioactivity and ADMET properties were also predicted to ratify the result. The compound asserted neither carcinogenic nor mutagenic activity and has high oral bioavailability. Hence, this synthesized novel compound Olanzapinium 2,5-dihydroxybenzoate recognized in the study possesses high potential as an effective antipsychotic compound, and can further be examined for its efficiency by in vivo studies. The synthesized compound was submitted to NCBI PubChem database using accession substance ID: 441329256. The crystal structure was submitted to CCDC (Cambridge Crystallographic Data Centre) with submission ID: 2010899.

Metabolism of the antipsychotic drug olanzapine by CYP3A43

1. Olanzapine is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. An intronic single nucleotide polymorphism (SNP) that highly significantly predicts increased olanzapine clearance (rs472660) was previously identified in the CYP3A43 gene, which encodes a cytochrome P450 enzyme. But until now there was no experimental evidence for the metabolism of olanzapine by the CYP3A43 enzyme. 2. In the present study we provide this evidence, together with a thorough analysis of olanzapine metabolism by all human CYP3A enzymes. We also rationalise our findings by molecular docking experiments. Moreover, we describe the activities of several CYP3A43 mutants and present the first enzymatic activity data for the CYP3A43.3 variant; with respect to prostate cancer, this polymorphic variant is associated with both increased risk and increased mortality. The catalytic properties of the wild type enzyme and the tumour mutant were analysed by molecular dynamics simulations, which fit very well with the observed experimental results. 3. Our findings suggest that the SNP rs472660 likely causes an increased CYP3A43 expression level and demonstrate that, depending on the substrate under study, the tumour mutant CYP3A43.3 can have increased activity in comparison to the wild type enzyme CYP3A43.1.

Early Lipid Metabolic Effects of the Anti-Psychotic Drug Olanzapine on Weight Gain and the Associated Gene Expression.

BackgroundAtypical antipsychotics such as olanzapine often cause metabolic side effects such as obesity and diabetes, leading to an increased risk of nonalcoholic fatty liver disease. The aim of the present study was to investigate the effects of olanzapine treatment on hepatic lipid metabolism and its possible relationship with adipose tissue status.MethodsUsing a female rat model, we investigated the effects of chronic olanzapine administration on the regulation of carbohydrate and lipid metabolism including lipid biosynthesis, oxidation, efflux, and lipolysis in liver and adipose tissue.ResultsThe body weight, liver mass and visceral adiposity after olanzapine treatment (2 mg/kg) for five weeks were not significantly different compared with vehicle controls. The serum level of triglycerides was higher in the vehicle controls than in olanzapine-treated rats. Unexpectedly, olanzapine treatment did not reduce glucose tolerance in our model. The expression of functional thermogenic protein uncoupling protein 1 (UCP1) was increased in brown adipose tissue (BAT) of the olanzapine group. Additionally, olanzapine treatment also reduced adipose inflammation in white adipose tissue (WAT). The transcription factor sterol regulatory element-binding protein (SREBP)-1c, a key early regulator of lipogenesis, was downregulated following olanzapine treatment. The expression of genes related to the triglycerides synthesis apparatus in the liver was upregulated in the olanzapine group. Olanzapine treatment induced genes involved in PPAR-α signaling and mitochondrial fatty acid oxidation in response to increased ATGL-mediated lipolysis in the liver.ConclusionTogether, our findings suggest a complicated link between olanzapine therapy and metabolic disturbance and may garner interest in assessing the action of antipsychotic-induced metabolic disturbances.

The negative impact of vitamin D on antipsychotic drug exposure may counteract its potential benefits in schizophrenia.

Patients with schizophrenia frequently show insufficient vitamin D levels, which are associated with somatic comorbidity and may contribute to psychopathology. For many reasons, vitamin D supplementation may be indicated for this patient cohort. However, there is growing evidence for a vitamin D-mediated increase of drug metabolism by induction of cytochrome P450 (CYP) 3A4. Hence, this study aimed to assess vitamin D's impact on both antipsychotic drug concentrations and psychopathology in a non-interventional manner. Totals of 107 serum concentrations of different antipsychotic drugs (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine and risperidone), 80 serum concentrations of vitamin D and psychopathological assessments were obtained from 80 patients with schizophrenia. The impact of Vitamin D on antipsychotic drug concentrations and symptomatology was assessed using a generalized linear model, path and correlation analyses. We observed a negative relationship between vitamin D and dose-adjusted antipsychotic drug concentrations, which was particularly pronounced for drugs which are predominantly metabolized via CYP3A4 (i.e., aripiprazole and quetiapine). A path analysis suggested a relieving effect of vitamin D on symptomatology which was, however, counteracted by its negative impact on antipsychotic drug levels. Finally, patients with vitamin D levels above the median exhibited a significantly higher proportion of therapeutically insufficient dose-normalized drug concentrations of aripiprazole and quetiapine. Despite vitamin D's potential benefits on physical and mental health, clinicians should be aware of its negative impact on blood concentrations of antipsychotics metabolized by CYP3A4 in patients with schizophrenia. Therefore, when considering its supplementation, therapeutic drug monitoring should be applied to guide dose adjustment.

The versatile behavior of diamond electrodes — Electrochemical examination of the anti-psychotic drug olanzapine (OL) oxidation as a model organic aqueous solution

The electrochemical degradation of dilute aqueous solutions of olanzapine (OL), using boron-doped diamond (BDD) anodes as electrocatalysts, was investigated. The studies were carried out in a single-compartment electrochemical cell at three different current densities (10, 30, and 50 mA cm−2), 25 °C, and 50 mg L−1 of OL in 0.05 M Na2SO4 pH (2.0, 4.0 and 6.0) as supporting electrolyte. The OL concentration and feasible by-products of the oxidized solution were monitored during the oxidation process using UV spectrophotometry, chemical oxygen demand (COD), total organic carbon (TOC), and high-performance liquid chromatography-mass spectrometry (HPLC-MS) techniques. Through voltametric studies, it was revealed that OL oxidation involved a direct oxidation stage, characterized by a current peak at +0.8 V (vs Ag/AgCl3M) that behaved as a quasi-reversible process, and an irreversible oxidation stage as well as an indirect oxidation step at +1.65 V (vs Ag/AgCl3M) mediated by physiosorbed ●OH radicals on BDD surface, which were formed by the discharge of water. The dependence of the peak current (ip), as well as the peak potential (Ep), with the potential sweep rate ν (mV s−1), showed that the oxidation depended on the diffusion of OL towards the BDD surface. By using a chronoamperometric analysis, a value of 6.6 × 10−4 cm2 s−1 was estimated for the diffusion coefficient of OL in 0.05 M Na2SO4 pH 2.0, confirming the transport effects. The results of UV and HPLC showed that the OL removal rate increased as the applied current density increased, although the COD and TOC data showed that a better oxidation is achieved at 30 mA cm−2. The results of HPLC-MS were consistent with the removal processes, involving both direct and indirect OL oxidation steps with BDD electrode. In any case, the results clearly confirmed the OL removal from the aqueous solution, achieving 80% of mineralization at applied current densities greater than 30 mA cm−2.