D2 occupancy

Objective: Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and dopamine D2 -receptor occupancy for oral and long-acting injectable (LAI) formulations. Data Sources: Databases were systematically searched for randomized controlled trials (RCTs) and uncontrolled trials concerning blood olanzapine levels in relation to clinical outcomes or D2 -receptor occupancy using MEDLINE (PubMed), Web of Science, PsycINFO, and Cochrane Library (March 2021, updated in December 2021)...

INTRODUCTION: Lumateperone is a novel antipsychotic medication that has recently received approval by the United States Food and Drug Administration for treatment of major depressive episodes of type I and II bipolar disorder. It is approved for use as monotherapy or as an adjunctive treatment to lithium or valproic acid. AREAS COVERED: Clinical trials performed with lumateperone for bipolar disorder were reviewed. Additionally, pharmacodynamic actions of lumateperone are reviewed...

This cross-sectional study aimed to assess Brazilian child caregivers' eating competence (EC) and their adherence to the division of responsibility (sDOR) in child feeding. The research had national coverage in all Brazilian regions. The sample comprised 549 caregivers of Brazilian children (24 up to 72 months) recruited by social media (snowball method). Data on sDOR and EC were collected using the sDOR.2-6yTM Portuguese-Brazil (sDOR.2-6y-BR) and ecSI2.0TM BR, both instruments validated to the Brazilian population...

The nose-to-brain (N2B) pathway has garnered attention because it transports drugs directly into the brain. Although recent studies have suggested the necessity of selective drug administration to the olfactory region for effective N2B drug delivery, the importance of delivering the formulation to the olfactory region and the detailed pathway involved in drug uptake in primates brain remain unclear. Here, we developed a combination system for N2B drug delivery comprising a proprietary mucoadhesive powder formulation and a dedicated nasal device (N2B-system) and evaluated it for nasal drug delivery to the brain in cynomolgus monkeys...

PURPOSE/OBJECTIVES: Academic metrics and clinical performance are necessary but alone insufficient in describing success in dental education. This paper identifies themes critical for dental student success as commonly cited by both dental students and faculty. METHODS: Dental faculty interviews and pre-doctoral D2/D3/D4 student focus groups at two dental institutions generated data for thematic analysis. Themes were individually identified then merged, compared, and contrasted to establish a definitive list of key themes reflected in student and faculty comments...

INTRODUCTION: Olanzapine is widely used for treating schizophrenia and bipolar I disorder. Due to its high pharmacokinetic variability, several population pharmacokinetic studies have been performed to identify factors contributing to the variability and thus facilitate individualized dosing. This review aims to provide a comprehensive overview of published population pharmacokinetic studies and explore potential covariates. METHODS: We systematically searched PubMed, Web of Science, and EMBASE databases from their inception to 31 December 2022...

Schizophrenia is a worldwide mental illness characterized by alterations at dopaminergic and glutamatergic synapses resulting in global dysconnectivity within and between brain networks. Impairments in inflammatory processes, mitochondrial functions, energy expenditure, and oxidative stress have been extensively associated with schizophrenia pathophysiology. Antipsychotics, the mainstay of schizophrenia pharmacological treatment and all sharing the common feature of dopamine D2 receptor occupancy, may affect antioxidant pathways as well as mitochondrial protein levels and gene expression...

After the worst mine-tailing dam disaster which occurred in Minas Gerais state, Brazil, it was necessary to understand the extent of the biodiversity loss. Thus, based on legal obligations, a monitoring of the fauna and flora along the Rio Doce basin was developed. From this large study, surprisingly, two undescribed psammophilous mayfly species were collected. Given the environmental disaster, and the particular concern with species that inhabiting sandy bottom, the two new species may be already threatened...

Protein translation is essential for some forms of synaptic plasticity. We used nucleus accumbens (NAc) medium spiny neurons (MSN), co-cultured with cortical neurons to restore excitatory synapses, to examine whether dopamine modulates protein translation in NAc MSN. FUNCAT was used to measure translation in MSNs under basal conditions and after disinhibiting excitatory transmission using the GABA A receptor antagonist bicuculline (2 hr). Under basal conditions, translation was not altered by the D1-class receptor (D1R) agonist SKF81297 or the D2-class receptor (D2R) agonist quinpirole...

Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain connectivity. Antipsychotics are the primary pharmacological treatment after more than sixty years after their introduction in therapy. Two findings hold true for all presently available antipsychotics. First, all antipsychotics occupy the dopamine D2 receptor (D2R) as an antagonist or partial agonist, even if with different affinity; second, D2R occupancy is the necessary and probably the sufficient mechanism for antipsychotic effect despite the complexity of antipsychotics' receptor profile...

BACKGROUND: Neural synchrony at gamma frequency (~40 Hz) is important for information processing and is disrupted in schizophrenia. From a drug development perspective, molecules that can improve local gamma synchrony are promising candidates for therapeutic development. HYPOTHESIS: Given their differentiated clinical profile, clozapine, and haloperidol may have distinct effects on local gamma synchrony engendered by 40 Hz click trains, the so-called auditory steady-state response (ASSR)...

INTRODUCTION: Treatment resistant schizophrenia (TRS), the lack of response to at least two antipsychotics administered at adequate dose and duration, epitomizes in psychiatry one of the most difficult-to-treat pathologies, epidemiologically relevant (affecting one-third of schizophrenia patients) and with severe consequences for the patients in terms of overall functioning. After 50 years, only one drug is approved for TRS: clozapine. Furthermore, a few patients do not respond even to clozapine and are indicated as clozapine-resistant patients...

BACKGROUND: Incident diabetes risk is inversely proportional to 25-hydroxyvitamin D [25(OH)D] levels among non-Hispanic white but is unclear among African American (AA) populations. Serum 25(OH)D2 may be an important component of total 25(OH)D among AA populations due to higher levels of melanin. OBJECTIVE: To assess the association of serum 25(OH)D with incident diabetes among AAs and stratify by detectable 25(OH)D2. DESIGN: Serum 25(OH)D2 and 25(OH)D3 were collected from 2000 to 2004 among AA participants in the Jackson Heart Study...

BACKGROUND: Successful osseointegration of endosteal dental implants has been attributed to implant design, including the macro-, micro- and nano- geometric properties. Based on current literature pertaining to implant design, the resultant cellular and bone healing response is unknown when the thread thickness of the implants is increased, resulting in an increased contact area in implants designed with healing chambers. The aim of this study was to evaluate the effect of two implant designs with different thread profiles on the osseointegration parameters and implant stability at 3- and 6-weeks in vivo using a well-established preclinical dog model...

PURPOSE/OBJECTIVES: This study explored key mental health measures as self-reported by pre-doctoral dental students enrolled in all four years of dental school and their relationships with a year in school and resilience. METHODS: This study utilized archival data from the National Collegiate Health Assessment (NCHA) survey administered in Fall 2020. This instrument is a compilation of validated measures assessing a broad spectrum of health-related behaviors, including nutrition, substance use, social relationships, and mental health...

The construction industry is an important pillar industry in China. It not only promotes the development of China's industry but also promotes the progress of society. It can be said that it has made great contributions to the development of China's economic construction. Issues such as sustainable development, green health, resource conservation, and environmental protection have become the most discussed topics, and it is imperative to implement green building management in the construction industry. Therefore, China has put forward the development concept of "green building," which puts the management of green building on the basis of traditional building, and pays more attention to the goal of energy saving, environmental protection, people-oriented and green innovation...

Objective: To assess exposure levels to electromagnetic fields (EMFs) among library workers in Japan, focusing on co-exposure to intermediate-frequency EMF (IF-EMF) and pulsed EMF, to propose a new epidemiological research methodology. Methods: The evaluated exposure sources were an electromagnetic type-electronic article surveillance gate (EM-EAS, IF-EMF (operating frequency 220 Hz-14 kHz)) and an activator/deactivator of anti-theft tags termed as "book check unit" (BCU, pulsed EMF)...

Schizophrenia has been conceptualized as a neurodevelopmental disorder with synaptic alterations and aberrant cortical-subcortical connections. Antipsychotics are the mainstay of schizophrenia treatment and nearly all share the common feature of dopamine D2 receptor occupancy, whereas glutamatergic abnormalities are not targeted by the presently available therapies. D-amino acids, acting as N-methyl-D-aspartate receptor (NMDAR) modulators, have emerged in the last few years as a potential augmentation strategy in those cases of schizophrenia that do not respond well to antipsychotics, a condition defined as treatment-resistant schizophrenia (TRS), affecting almost 30-40% of patients, and characterized by serious cognitive deficits and functional impairment...

LB-102 is an N-methylated analogue of amisulpride under development to treat schizophrenia. LB-102 was evaluated in a Phase 1, double-blind, placebo-controlled, clinical study to evaluate safety and pharmacokinetics. This was a first-in-human study examining single and multiple doses of LB-102 administered orally in 64 healthy volunteers. Dosing in the single ascending dose (SAD) portion of the study was initially planned to be 50, 100, 200, and 400 mg, with doses in the multiple ascending dose (MAD) portion to be determined based on observations in the SAD portion...

The dopamine blockade by antipsychotics trigger subjective dysphoria. Compared with D2 antagonists, aripiprazole, a D2 partial agonist, was expected to produce a different experience. Indeed, a previous study reported no relationship between the D2 receptor occupancy by aripiprazole and subjective dysphoria, while the D2 receptor occupancy by antagonists was associated with negative subjective experiences. This study revisited the relationship in patients treated with aripiprazole by using an inhibitory Emax model, which enables the individual drug-free binding potential and D2 receptor occupancy to be properly estimated...