Kanae Ito, Masashi Harada, Norifumi L Yamada, Kenji Kudo, Hiroyuki Aoki, Toshiji Kanaya
We performed H2 O and D2 O double-contrast neutron reflectivity measurements on ∼25 nm thick Nafion thin films on hydrophilic and hydrophobic carbon in water and 80% relative humidity vapor to investigate the depth profile of the water and Nafion distribution. We found a dense Nafion layer at the air or water interface regardless of the carbon hydrophilicity. On the other hand, a water-rich Nafion dense layer was observed at the carbon interface only for hydrophilic carbon. The double-contrast measurements provided quantitative information about the depth profile but simultaneously indicated that the sum of the volume occupancies of water and Nafion in the film was less than unity...
October 21, 2020: Langmuir: the ACS Journal of Surfaces and Colloids
Hitoshi Watanabe, Kyoji Ishida, Masanori Yamamoto, Masakuni Horiguchi, Yoshiaki Isobe
Clozapine-like compound without agranulocytosis risk is need to cure the treatment resistant schizophrenia (TRS). We discovered (S)-3 as Clozapine-like dopamine D2 /D1 receptor selectivity and improved reactive metabolites formation profile by the modification of piperazine moiety in Clozapine. The optimization of (S)-3 gave compound 5 to be best compound (approximately 10-fold stronger affinity for D2 /D1 receptor and similar D2 /D1 selectivity ratio with Clozapine). Clozapine-like D2 /D1 receptor occupancy profile was proved by in vivo evaluation...
September 22, 2020: Bioorganic & Medicinal Chemistry Letters
Hironori Nishibe, Amane Tateno, Takeshi Sakayori, Masahiro Yamamoto, WooChan Kim, Hiroyoshi Kakuyama, Yoshiro Okubo
BACKGROUND: Transdermal antipsychotic patch formulations offer potential benefits, including improved adherence. This study investigated the striatal dopamine D2 receptor occupancy with daily blonanserin transdermal patch application. METHODS: This open-label, Phase 2 study enrolled 18 Japanese outpatients (20 to <65 years) with schizophrenia (DSM-IV-TR criteria; total Positive and Negative Syndrome Scale [PANSS] score <120 at screening) treated with blonanserin 8 mg or 16 mg tablets...
September 16, 2020: International Journal of Neuropsychopharmacology
J N de Boer, A E Voppel, S G Brederoo, F N K Wijnen, I E C Sommer
Language disturbances are key aberrations in schizophrenia. Little is known about the influence of antipsychotic medication on these symptoms. Using computational language methods, this study evaluated the impact of high versus low dopamine D2 receptor (D2R) occupancy antipsychotics on language disturbances in 41 patients with schizophrenia, relative to 40 healthy controls. Patients with high versus low D2R occupancy antipsychotics differed by total number of words and type-token ratio, suggesting medication effects...
September 7, 2020: NPJ Schizophrenia
Robert Lew, Cristian C Constantinescu, Daniel Holden, Richard E Carson, Vincent Carroll, Gerald Galluppi, Kenneth S Koblan, Seth C Hopkins
RATIONALE: Drugs that rapidly increase dopamine levels have an increased risk of abuse. Dasotraline (DAS) is a dopamine and norepinephrine reuptake inhibitor characterized by slow oral absorption with low potential for abuse. However, it remains unclear whether intravenous (i.v.) administration would facilitate the rapid elevation of dopamine levels associated with stimulant drugs. OBJECTIVE: To assess the kinetics of DAS across the blood-brain barrier and time to onset of dopamine transporters (DAT) inhibition...
August 19, 2020: Psychopharmacology
Shin Kurose, Yu Mimura, Hiroyuki Uchida, Keisuke Takahata, Euitae Kim, Takefumi Suzuki, Masaru Mimura, Hiroyoshi Takeuchi
OBJECTIVE: The objective of this study was to examine the extent of possible dissociation in pharmacokinetic decay between central dopamine D₂ receptor occupancy with antipsychotics and their peripheral blood concentrations. DATA SOURCES: MEDLINE and Embase were searched using the following keywords: (positron emission tomography OR PET OR single-photon emission computed tomography OR SPECT) AND (dopamine OR D2) AND (receptor* OR occupanc*) AND antipsychotic*, with a limitation of English language (last search: December 14, 2019)...
July 28, 2020: Journal of Clinical Psychiatry
Yukiko Masaki, Yuto Kashiwagi, Takemi Rokugawa, Miwa Ito, Hitoshi Iimori, Kohji Abe
Pharmacological magnetic resonance imaging (phMRI) allows the visualization of brain pharmacological effects of drugs using functional MRI (fMRI). phMRI can help us facilitate central nervous system (CNS) drug development. However, there have been few studies demonstrating the dose-relationship of the fMRI response induced by CNS drugs to underlying target-engagement or behavioral efficacy. To clarify these relationships, we examined receptor occupancy measurements using positron emission tomography (PET) (n = 3~5), fMRI (n = 5~8) and a cataleptic behavior (n = 6) with raclopride, a dopamine D2 receptor antagonist (8, 20, and 200 μg/kg) on Wistar rats...
July 9, 2020: Synapse
Evelien Zoons, Marina A J Tijssen, Yasmine E M Dreissen, Marenka Smit, Jan Booij
Purpose: The pathophysiology of cervical dystonia (CD) is thought to be related to changes in dopamine and serotonin levels in the brain. We performed a double-blind trial with escitalopram (selective serotonin reuptake inhibitor; SSRI) in patients with CD. Here, we report on changes in dopamine D2/3 receptor (D2/3R), dopamine transporter (DAT) and serotonin transporter (SERT) binding potential (BPND ) after a six-week treatment course with escitalopram or placebo. Methods: CD patients had [123I]FP-CIT SPECT (I-123 fluoropropyl carbomethoxy-3 beta-(4-iodophenyltropane) single-photon emission computed tomography) scans, to quantify extrastriatal SERT and striatal DAT, and [123I]IBZM SPECT (I-123 iodobenzamide SPECT) scans to quantify striatal D2/3R BPND before and after six weeks of treatment with either escitalopram or placebo...
June 8, 2020: Biomolecules
Ryosuke Arakawa, Akihiro Takano, Christer Halldin
Positron emission tomography (PET) is a non-invasive imaging method to measure the molecule in vivo. PET imaging can evaluate the central nervous system drugs as target engagement in the human brain. For antipsychotic drugs, adequate dopamine D2 receptor occupancy ("therapeutic window") is reported to be from 65%-70% to 80% to achieve the antipsychotic effect without extrapyramidal symptoms. For antidepressants, the clinical threshold of serotonin transporter (5-HTT) occupancy is reported to be 70%-80% although the relation between the side effect and 5-HTT occupancy has not yet been established...
May 28, 2020: Neuropsychopharmacology Reports
Kelly Smart, Jean-Dominique Gallezot, Nabeel Nabulsi, David Labaree, Ming-Qiang Zheng, Yiyun Huang, Richard E Carson, Ansel T Hillmer, Patrick D Worhunsky
Development of medications selective for dopamine D2 or D3 receptors is an active area of research in numerous neuropsychiatric disorders including addiction and Parkinson's disease. The positron emission tomography (PET) radiotracer [11 C]-(+)-PHNO, an agonist that binds with high affinity to both D2 and D3 receptors, has been used to estimate relative receptor subtype occupancy by drugs based on a priori knowledge of regional variation in the expression of D2 and D3 receptors. The objective of this work was to use a data-driven independent component analysis (ICA) of receptor blocking scans to separate D2 -and D3 -related signal in [11 C]-(+)-PHNO binding data in order to improve the precision of subtype specific measurements of binding and occupancy...
March 19, 2020: NeuroImage
Rick A Adams, Michael Moutoussis, Matthew M Nour, Tarik Dahoun, Declan Lewis, Benjamin Illingworth, Mattia Veronese, Christoph Mathys, Lieke de Boer, Marc Guitart-Masip, Karl J Friston, Oliver D Howes, Jonathan P Roiser
Choosing actions that result in advantageous outcomes is a fundamental function of nervous systems. All computational decision-making models contain a mechanism that controls the variability of (or confidence in) action selection, but its neural implementation is unclear-especially in humans. We investigated this mechanism using two influential decision-making frameworks: active inference (AI) and reinforcement learning (RL). In AI, the precision (inverse variance) of beliefs about policies controls action selection variability-similar to decision 'noise' parameters in RL-and is thought to be encoded by striatal dopamine signaling...
February 21, 2020: Cerebral Cortex
Cherie Blackwell, Kathy Cary, Kami Holst, Kristen Mandle, Lori Dryg, Susan Clemens, Jon H Lemke, Sarah Castro, Emma Hendricks, Ryan Kelly
IMPORTANCE: Previous research has calculated normative data for the Dynavision D2 Visuomotor Training (D2) System among healthy athletes to understand concussion management, but to date no studies have identified the norms for healthy adults over a large age range (18-80 yr) for physical response speed. OBJECTIVE: To provide normative data for the D2 for physical response speed in adults ages 18-80 yr. DESIGN: Cross-sectional, descriptive study to obtain normative data on physical response speed using the D2 for adults in age categories 18-40, 41-60, and 61-80 yr...
January 2020: American Journal of Occupational Therapy: Official Publication of the American Occupational Therapy Association
Lars Hunger, Arvind Kumar, Robert Schmidt
The neuromodulator dopamine plays a key role in motivation, reward-related learning, and normal motor function. The different affinity of striatal D1 and D2 dopamine receptor types has been argued to constrain the D1 and D2 signaling pathways to phasic and tonic dopamine signals, respectively. However, this view assumes that dopamine receptor kinetics are instantaneous so that the time courses of changes in dopamine concentration and changes in receptor occupation are basically identical. Here we developed a neurochemical model of dopamine receptor binding taking into account the different kinetics and abundance of D1 and D2 receptors in the striatum...
April 1, 2020: Journal of Neuroscience
Ragy R Girgis, Andy Forbes, Anissa Abi-Dargham, Mark Slifstein
The objective of this study (NCT01854944) was to assess D2 /D3 , 5-HT1A , 5-HT2A and serotonin transporter (SERT) occupancies of brexpiprazole in adult subjects with schizophrenia in order to identify the in vivo pharmacologic profile that may be relevant to the antipsychotic, antidepressant, and side effect profiles of the drug. Subjects were grouped into three independent cohorts of four subjects each. All subjects underwent positron emission tomography (PET) scans with two different radiotracers at baseline prior to brexpiprazole administration, and again on Day 10 after daily doses of either 4 mg (Cohorts 1 and 2), or 1 mg (Cohort 3)...
April 2020: Neuropsychopharmacology
Mark Slifstein, Anissa Abi-Dargham, Ragy R Girgis, Raymond F Suckow, Thomas B Cooper, Chaitanya R Divgi, Pierre Sokoloff, Ludovic Leriche, Patrick Carberry, Shunichi Oya, Simon K Joseph, Marlène Guiraud, Agnès Montagne, Valérie Brunner, Florence Gaudoux, Françoise Tonner
RATIONALE: F17464, a dopamine D3 receptor antagonist with relatively high D3 selectivity (70 fold vs D2 in vitro), exhibits an antipsychotic profile in preclinical studies, and therapeutic efficacy was demonstrated in a randomized placebo-controlled clinical trial in patients with schizophrenia (Bitter et al. Neuropsychopharmacology 44(11):1917-1924, 2019). OBJECTIVE: This open-label study in healthy male subjects aimed at characterizing F17464 binding to D3/D2 receptors and the time course of receptor occupancy using positron emission tomography (PET) imaging with a D3-preferring tracer, [11 C]-(+)-PHNO...
November 26, 2019: Psychopharmacology
Tanja Veselinović, Martin Scharpenberg, Martin Heinze, Joachim Cordes, Bernd Mühlbauer, Georg Juckel, Eckart Rüther, Michael Paulzen, Ekkehard Haen, Christoph Hiemke, Jürgen Timm, Gerhard Gründer
BACKGROUND: Impaired subjective well-being in schizophrenia patients treated with antipsychotics has often been linked inter alia to the antidopaminergic effects of medication. Thus, it is important to capture the association between striatal dopamine D2 receptor occupancy (D2-RO) and global subjective well-being. We examined this association using data from our multicenter, randomized, double-blind Neuroleptic Strategy Study (NeSSy). METHODS: An innovative double randomization process was used for allocation of patients to the specific treatment groups...
November 2019: Journal of Clinical Psychopharmacology
Tuulia Huhtala, Pekka Poutiainen, Jussi Rytkönen, Kimmo Lehtimäki, Teija Parkkari, Iiris Kasanen, Anu J Airaksinen, Teija Koivula, Patrick Sweeney, Outi Kontkanen, John Wityak, Celia Dominiquez, Larry C Park
PURPOSE: Dopamine receptors are involved in pathophysiology of neuropsychiatric diseases, including Huntington's disease (HD). PET imaging of dopamine D2 receptors (D2R) in HD patients has demonstrated 40% decrease in D2R binding in striatum, and D2R could be a reliable quantitative target to monitor disease progression. A D2/3R antagonist, [18 F] fallypride, is a high-affinity radioligand that has been clinically used to study receptor density and occupancy in neuropsychiatric disorders...
August 5, 2019: EJNMMI Radiopharmacy and Chemistry
Béla Kiss, Zsolt Némethy, Károly Fazekas, Dalma Kurkó, István Gyertyán, Katalin Sághy, István Laszlovszky, Bence Farkas, Norbert Kirschner, Etelka Bolf-Terjéki, Ottilia Balázs, Balázs Lendvai
Introduction : Cariprazine, a dopamine D3 -preferring D3 /D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, has two major human metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR). The metabolite pharmacology was profiled to understand the contribution to cariprazine efficacy. Methods: In vitro receptor binding and functional assays, electrophysiology, animal models, microdialysis, and kinetic-metabolism approaches were used to characterize the pharmacology of DCAR and DDCAR...
2019: Drug Design, Development and Therapy
Ružica Jurakić Tončić, Anamaria Balić, Borna Pavičić, Kristina Žužul, Mikela Petković, Lucija Bartolić, Suzana Ljubojević Hadžavdić
Airborne contact dermatitis (ACD) is a frequent condition, and there has been increasing recognition of the occupational origin of airborne contact dermatitis. ACD caused by drugs is often occupation-related and occurs mainly in healthcare workers who use the drugs for therapeutic aims and employees of pharmaceutical industries involved in the production of the drugs (1). Omeprazole (OM) is a proton pump inhibitor from the benzimidazole group used for treatment of gastric acid-related disorders (2). A 52-years-old female chemist had been working in a pharmaceutical company for 20 years...
September 2019: Acta Dermatovenerologica Croatica: ADC
Jonas E Svensson, Martin Schain, Pontus Plavén-Sigray, Simon Cervenka, Mikael Tiger, Magdalena Nord, Christer Halldin, Lars Farde, Johan Lundberg
[11 C]raclopride is a well established PET tracer for the quantification of dopamine 2/3 receptors (D2/3 R) in the striatum. Outside of the striatum the receptor density is up to two orders of magnitude lower. In contrast to striatal binding, the characteristics of extrastriatal [11 C]raclopride binding quantification has not been thoroughly described. Still, binding data for e.g., neocortex is frequently reported in the scientific literature. Here we evaluate the validity and reliability of extrastriatal [11 C]raclopride binding quantification...
August 29, 2019: NeuroImage
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"