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Clozapine

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https://www.readbyqxmd.com/read/28343762/clozapine-and-incidence-of-myocarditis-and-sudden-death-long-term-australian-experience
#1
Arshad A Khan, Asma Ashraf, David Baker, Mohammed S Al-Omary, Lindsay Savage, Avedis Ekmejian, Rajinder Singh Harjit Singh, Stephen Brienesse, Tazeen Majeed, Tracy Gordon, Vincent Drinkwater, Nicholas J Collins
BACKGROUND: Clozapine is the cornerstone of therapy for refractory schizophrenia; however, the potential for cardiotoxicity is an important limitation in its use. In the current analysis we sought to evaluate the long term cardiac outcomes of clozapine therapy. METHODS: All-cause mortality, incidence of sudden death and time to myocarditis were assessed in a cohort of patients maintained on clozapine between January 2009 and December 2015. All patients had regular electrocardiograms, complete blood count, clozapine levels and echocardiography as part of a formal protocol...
March 6, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28341945/translational-value-of-drug-discrimination-with-typical-and-atypical-antipsychotic-drugs
#2
Joseph H Porter, Kevin A Webster, Adam J Prus
This chapter focuses on the translational value of drug discrimination as a preclinical assay for drug development. In particular, the importance of two factors, i.e., training dose and species, for drug discrimination studies with the atypical antipsychotic clozapine is examined. Serotonin receptors appear to be an important pharmacological mechanism mediating clozapine's discriminative cue in both rats and mice, although differences are clearly evident as antagonism of cholinergic muscarinic receptors is important in rats at a higher training dose (5...
March 25, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28340122/potential-role-of-patients-cyp3a-status-in-clozapine-pharmacokinetics
#3
Katalin Tóth, Gábor Csukly, Dávid Sirok, Ales Belic, Ádám Kiss, Edit Háfra, Máté Déri, Ádám Menus, István Bitter, Katalin Monostory
Background: The atypical antipsychotic clozapine is effective in treatment-resistant schizophrenia; however, the success or failure of clozapine therapy is substantially affected by the variables that impact the clozapine blood concentration. Thus, elucidating the inter-individual differences in clozapine pharmacokinetics can facilitate the personalized therapy. Methods: Since potential role in clozapine metabolism is assigned to CYP1A2, CYP2C19, CYP2D6 and CYP3A enzymes, the association between the patients' CYP-status (CYP genotypes, CYP expression) and clozapine clearance was evaluated in 92 psychiatric patients...
March 18, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28335437/effect-of-clozapine-on-dna-methylation-in-peripheral-leukocytes-from-patients-with-treatment-resistant-schizophrenia
#4
Makoto Kinoshita, Shusuke Numata, Atsushi Tajima, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Shinya Watanabe, Hidehiro Umehara, Shinji Shimodera, Takanobu Nakazawa, Masataka Kikuchi, Akihiro Nakaya, Hitoshi Hashimoto, Issei Imoto, Ryota Hashimoto, Tetsuro Ohmori
Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study...
March 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28333365/clozapine-combined-with-different-antipsychotic-drugs-for-treatment-resistant-schizophrenia
#5
REVIEW
Sarah Barber, Uwaila Olotu, Martina Corsi, Andrea Cipriani
BACKGROUND: Between 40% and 70% of people with treatment-resistant schizophrenia do not respond to clozapine, despite adequate blood levels. For these people, a number of treatment strategies have emerged, including the prescription of a second anti-psychotic drug in combination with clozapine. OBJECTIVES: To determine the clinical effects of various clozapine combination strategies with antipsychotic drugs in people with treatment-resistant schizophrenia both in terms of efficacy and tolerability...
March 23, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28331504/clozapine-treatment-and-cannabis-use-in-adolescents-with-psychotic-disorders-a-retrospective-cohort-chart-review
#6
Sephora M Tang, Aylar Ansarian, Darren B Courtney
OBJECTIVES: To examine the association between clozapine treatment and frequency of cannabis use in adolescents with co-occurring psychotic and cannabis use disorder in a retrospective cohort chart review. METHOD: We conducted a retrospective cohort chart review of patients diagnosed with a psychotic disorder and concurrent cannabis use disorder admitted to a tertiary care youth inpatient unit from 2010-2012. Longitudinal exposure and outcome data was coded month-by-month...
2017: Journal of the Canadian Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/28328789/clotiapine-monotherapy-in-a-patient-with-clozapine-resistant-schizophrenia
#7
Chia-Hung Lin, Hsien-Yuan Lane
No abstract text is available yet for this article.
March 21, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28325790/dopamine-terminals-from-the-ventral-tegmental-area-gate-intrinsic-inhibition-in-the-prefrontal-cortex
#8
William C Buchta, Stephen V Mahler, Benjamin Harlan, Gary S Aston-Jones, Arthur C Riegel
Spike frequency adaptation (SFA or accommodation) and calcium-activated potassium channels that underlie after-hyperpolarization potentials (AHP) regulate repetitive firing of neurons. Precisely how neuromodulators such as dopamine from the ventral tegmental area (VTA) regulate SFA and AHP (together referred to as intrinsic inhibition) in the prefrontal cortex (PFC) remains unclear. Using whole cell electrophysiology, we measured intrinsic inhibition in prelimbic (PL) layer 5 pyramidal cells of male adult rats...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28324647/metabolism-and-distribution-of-clozapine-n-oxide-implications-for-nonhuman-primate-chemogenetics
#9
Jessica Raper, J Scott Daniels, Ryan D Morrison, Leonard Howell, Jocelyne Bachevalier, Thomas Wichmann, Adriana Galvan
The use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in neuroscience has rapidly expanded in rodent studies, but has lagged behind in nonhuman primate (NHP) experiments, slowing the development of this method for therapeutic use in humans. One reason for the slow adoption of DREADD technology in primates is that the pharmacokinetic properties and bioavailability of clozapine-n-oxide (CNO), the most commonly used ligand for human muscarinic (hM) DREADDs, are not fully described in primates...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28323458/clozapine-related-tachycardia-in-an-adolescent-with-treatment-resistant-early-onset-schizophrenia
#10
Venkata Kolli, Dalton Bourke, Jeannie Ngo, Maxwell J Luber, Barbara J Coffey
No abstract text is available yet for this article.
March 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28322891/effect-of-antipsychotics-on-mitochondrial-bioenergetics-of-rat-ovarian-theca-cells
#11
Ekramy Elmorsy, Ayat Al-Ghafari, Amal Misbah Aggour, Soaad Mohamed Mosad, Raheela Khan, Saad Amer
BACKGROUND: Antipsychotics (APs) are widely prescribed drugs, which are well known to cause reproductive adverse effects through mechanisms yet to be determined. The purpose of this study was to investigate the effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells as a possible mechanism of reproductive toxicity. METHODS: Isolated rat's theca interstitial cells (TICs) were treated with two typical (chlorpromazine [CPZ] and haloperidol [HAL]) and two atypical APs (risperidone [RIS] and clozapine [CLZ])...
March 17, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28322273/neuregulin-2-ablation-results-in-dopamine-dysregulation-and-severe-behavioral-phenotypes-relevant-to-psychiatric-disorders
#12
L Yan, A Shamir, M Skirzewski, E Leiva-Salcedo, O B Kwon, I Karavanova, D Paredes, O Malkesman, K R Bailey, D Vullhorst, J N Crawley, A Buonanno
Numerous genetic and functional studies implicate variants of Neuregulin-1 (NRG1) and its neuronal receptor ErbB4 in schizophrenia and many of its endophenotypes. Although the neurophysiological and behavioral phenotypes of NRG1 mutant mice have been investigated extensively, practically nothing is known about the function of NRG2, the closest NRG1 homolog. We found that NRG2 expression in the adult rodent brain does not overlap with NRG1 and is more extensive than originally reported, including expression in the striatum and medial prefrontal cortex (mPFC), and therefore generated NRG2 knockout mice (KO) to study its function...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28322236/the-role-of-mesolimbic-reward-neurocircuitry-in-prevention-and-rescue-of-the-activity-based-anorexia-aba-phenotype-in-rats
#13
Claire J Foldi, Laura K Milton, Brian J Oldfield
Patients suffering anorexia nervosa (AN) become anhedonic; unable or unwilling to derive normal pleasures and avoid rewarding outcomes, most profoundly in food intake. The activity-based anorexia (ABA) model recapitulates many of the characteristics of the human condition, including anhedonia, and allows investigation of the underlying neurobiology of AN. The potential for increased neuronal activity in reward/hedonic circuits to prevent and rescue weight loss is investigated in this model. The mesolimbic pathway extending from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) was activated using a dual viral strategy, involving retrograde transport of Cre (CAV2-Cre) to the VTA and coincident injection of DREADD receptors (AAV-hSyn-DIO-hM3D(Gq)-mCherry)...
March 21, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28314679/an-analysis-of-the-rewarding-and-aversive-associative-properties-of-nicotine-in-the-neonatal-quinpirole-model-effects-on-glial-cell-line-derived-neurotrophic-factor-gdnf
#14
Russell W Brown, Seth L Kirby, Adam R Denton, John M Dose, Elizabeth D Cummins, Wesley Drew Gill, Katherine C Burgess
This study analyzed the associative properties of nicotine in a conditioned place preference (CPP) paradigm in adolescent rats neonatally treated with quinpirole (NQ) or saline (NS). NQ produces dopamine D2 receptor supersensitivity that persists throughout the animal's lifetime, and therefore has relevance towards schizophrenia. In two experiments, rats were ip administered quinpirole (1mg/kg) or saline from postnatal day (P)1-21. After an initial preference test at P42-43, animals were conditioned for eight consecutive days with saline or nicotine (0...
March 14, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28303200/atypical-neuroleptic-malignant-syndrome-associated-with-use-of-clozapine
#15
Quevedo-Florez Leonardo, Granada-Romero Juliana, Camargo-Arenas Juan Fernando
The Neuroleptic Malignant Syndrome (NMS) is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine...
2017: Case Reports in Emergency Medicine
https://www.readbyqxmd.com/read/28297593/clinical-effectiveness-and-cognitive-impact-of-electroconvulsive-therapy-for-schizophrenia-a-large-retrospective-study
#16
Tyler S Kaster, Zafiris J Daskalakis, Daniel M Blumberger
OBJECTIVE: To determine the clinical effectiveness and cognitive impact of electroconvulsive therapy (ECT) in a large clinical sample of patients with schizophrenia and explore factors associated with treatment response and transient cognitive impairment. METHODS: We examined the clinical records of 144 patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were treated at an academic mental health hospital from October 2009 to August 2014...
March 14, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28291036/potential-mechanisms-of-hematological-adverse-drug-reactions-in-patients-receiving-clozapine-in-combination-with-proton-pump-inhibitors
#17
Michał Wiciński, Mateusz M Węclewicz, Mateusz Miętkiewicz, Bartosz Malinowski, Elżbieta Grześk, Joanna Klonowska
Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis...
March 2017: Journal of Psychiatric Practice
https://www.readbyqxmd.com/read/28283227/clozapine-as-the-most-efficacious-antipsychotic-for-activating-erk-1-2-kinases-role-of-5-ht2a-receptor-agonism
#18
Stefano Aringhieri, Shivakumar Kolachalam, Claudio Gerace, Marco Carli, Valeria Verdesca, Maria Giulia Brunacci, Chiara Rossi, Chiara Ippolito, Anna Solini, Giovanni U Corsini, Marco Scarselli
Antipsychotics (APDs) are divided into first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) based on the concept that SGAs have reduced motor side effects. With this premise, this study examined in HeLa and other cell lines the effects of different APDs on the activation of ERK1/2 (Extracellular signal-regulated kinases) and AKT (Protein Kinase B) kinases, which may be affected in schizophrenia and bipolar disorder. Among the SGAs, Clozapine clearly resulted as the most effective drug inducing ERK1/2 phosphorylation with potency in the low micromolar range...
March 7, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28281681/chemogenetic-stimulation-of-the-hypoglossal-neurons-improves-upper-airway-patency
#19
Thomaz Fleury Curado, Kenneth Fishbein, Huy Pho, Michael Brennick, Olga Dergacheva, Luiz U Sennes, Luu V Pham, Ellen E Ladenheim, Richard Spencer, David Mendelowitz, Alan R Schwartz, Vsevolod Y Polotsky
Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28279926/determination-of-drugs-in-plasma-samples-by-disposable-pipette-extraction-with-c18-bsa-phase-and-liquid-chromatography-tandem-mass-spectrometry
#20
Mônia Ap Lemos Pinto, Israel D de Souza, Maria Eugênia C Queiroz
This work describes restricted access material (RAM) constituted of porous octadecylsilane particles with the outer surface covered with bovine serum albumin (C18-BSA) as a stationary phase to extract drugs from plasma samples by disposable pipette extraction (DPX) for further analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The C18-BSA phase simultaneously excluded macromolecules by chemical diffusion barrier (BSA network) and enrichment of the interior phase (C18) with drug traces by sorption...
March 1, 2017: Journal of Pharmaceutical and Biomedical Analysis
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