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https://www.readbyqxmd.com/read/28729810/the-interplay-of-electrode-and-bio-materials-in-a-redox-cycling-based-clozapine-sensor
#1
Thomas E Winkler, Robert Dietrich, Eunkyoung Kim, Hadar Ben-Yoav, Deanna L Kelly, Gregory F Payne, Reza Ghodssi
We investigate gold, TiN, and platinum in combination with a chitosan-catechol-based redox-cycling system (RCS) for electrochemical detection of the antipsychotic clozapine. We have previously demonstrated the RCS for detection of clozapine in serum, but challenges remain regarding low signal-to-noise ratios. This can be mitigated by selection of electrode materials with beneficial surface morphologies and/or compositions. We employ cyclic voltammetry to assess the redox current generated by clozapine, and differentiate solely surface-area-based effects from clozapine-specific ones using a standard redox couple...
June 2017: Electrochemistry Communications
https://www.readbyqxmd.com/read/28721057/safety-tolerability-and-risks-associated-with-first-and-second-generation-antipsychotics-a-state-of-the-art-clinical-review
#2
REVIEW
Marco Solmi, Andrea Murru, Isabella Pacchiarotti, Juan Undurraga, Nicola Veronese, Michele Fornaro, Brendon Stubbs, Francesco Monaco, Eduard Vieta, Mary V Seeman, Christoph U Correll, André F Carvalho
Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients - psychosocial functioning, quality of life, and recovery...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28712880/the-role-of-oxidative-stress-in-antipsychotics-induced-ovarian-toxicity
#3
Ekramy Elmorsy, Ayat Al-Ghafari, Amal Misbah Aggour, Raheela Khan, Saad Amer
This study tested the hypothesis that oxidative stress could be an underlying mechanism for APs-induced ovarian cytotoxicity and reproductive dysfunction. Rat ovarian theca interstitial cells (TICs) were isolated and treated with four APs [chlorpromazine (CPZ), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ)]. MTT assay was used to test the effects of these antipsychotics on TICs viability and to estimate their 50% inhibitory concentrations (IC50s). The effects of APs (IC50s and 1μM concentrations) on the activities of caspases-3, -8 and -9, reactive oxygen species (ROS) production, total intracellular glutathione and lipid peroxidation (LPO) in TICs were assessed...
July 13, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28711601/catecholaminergic-a1-c1-neurons-contribute-to-the-maintenance-of-upper-airway-muscle-tone-but-may-not-participate-in-nrem-sleep-related-depression-of-these-muscles
#4
Irma Rukhadze, Nancy J Carballo, Sathyajit S Bandaru, Atul Malhotra, Patrick M Fuller, Victor B Fenik
Neural mechanisms of obstructive sleep apnea, a common sleep-related breathing disorder, are incompletely understood. Hypoglossal motoneurons, which provide tonic and inspiratory activation of genioglossus (GG) muscle (a major upper airway dilator), receive catecholaminergic input from medullary A1/C1 neurons. We aimed to determine the contribution of A1/C1 neurons in control of GG muscle during sleep and wakefulness. To do so, we placed injections of a viral vector into DBH-cre mice to selectively express the hMD4i inhibitory chemoreceptors in A1/C1 neurons...
July 12, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28705535/clozapine-blockade-of-mk-801-induced-learning-memory-impairment-in-the-mepm-role-of-5-ht1a-receptors-and-hippocampal-bdnf-levels
#5
Ximena López Hill, Analía Richeri, María Cecilia Scorza
Cognitive impairment associated with schizophrenia (CIAS) is highly prevalent and affects the overall functioning of patients. Clozapine (Clz), an atypical antipsychotic drug, significantly improves CIAS although the underlying mechanisms remain under study. The role of the 5-HT1A receptor (5-HT1A-R) in the ability of Clz to prevent the learning/memory impairment induced by MK-801 was investigated using the modified elevated plus-maze (mEPM) considering the Transfer latency (TL) as an index of spatial memory...
July 10, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28704228/patient-attitudes-to-clozapine-initiation
#6
Siobhan H Gee, Sukhwinder S Shergill, David M Taylor
Clozapine is widely underused. No study has assessed views of patients suitable for, but not yet receiving, clozapine. We aimed to assess views of clozapine in patients eligible for clozapine but not yet prescribed it by conducting semistructured interviews with acutely unwell hospital in-patients. We interviewed 61 of 116 eligible patients and 50 (82%) answered all questions. At interview, 33 (54%) of 61 participants had heard of clozapine and 17 (30%) of 57 participants said they would take it if asked. Overall, 31 (57%) of 54 respondents said blood testing would not preclude them taking clozapine...
July 12, 2017: International Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28703015/guidelines-for-the-pharmacotherapy-of-schizophrenia-in-adults
#7
Gary Remington, Donald Addington, William Honer, Zahinoor Ismail, Thomas Raedler, Michael Teehan
OBJECTIVE: The present guidelines address the pharmacotherapy of schizophrenia in adults across different stages, phases, and symptom domains. METHOD: Guidelines were developed using the ADAPTE process, which takes advantage of existing guidelines. Six guidelines were identified for adaptation, with recommendations extracted from each. For those specific to the pharmacotherapy of schizophrenia in adults, a working group selected between guidelines and recommendations to create an adapted guideline...
January 1, 2017: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
https://www.readbyqxmd.com/read/28688742/effects-of-adjunctive-fluvoxamine-on-metabolic-parameters-and-psychopathology-in-clozapine-treated-patients-with-schizophrenia-a-12-week-randomized-double-blind-placebo-controlled-study
#8
Mong-Liang Lu, Tzu-Ting Chen, Po-Hsiu Kuo, Ching-Chi Hsu, Chun-Hsin Chen
OBJECTIVE: Numerous studies have demonstrated that fluvoxamine has considerable pharmacokinetic and pharmacodynamic interactions with clozapine. We conducted a 12-week, randomized, double-blind, placebo-controlled study to evaluate the effects of fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia. METHODS: We recruited 85 patients who received a DSM-IV diagnosis of schizophrenia. Eligible patients were randomized to receive fluvoxamine 50mg/day plus clozapine 100mg/day or clozapine 300mg/day...
July 5, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28684394/tg-th-cre-fi172gsat-th-cre-defines-neurons-that-are-required-for-full-hypercapnic-and-hypoxic-reflexes
#9
Jenny J Sun, Russell S Ray
The catecholaminergic system has been implicated in many facets of breathing control and offers an important target to better comprehend the underlying etiologies of both developmental and adult respiratory pathophysiologies. Here we used a noninvasive DREADD based pharmaco-genetic approach to acutely perturb Tg(Th-Cre)FI172Gsat (Th-Cre) defined neurons in awake and unrestrained mice in an attempt to characterize catecholaminergic function in breathing. We report that clozapine-N-oxide (CNO)-DREADD mediated inhibition of Th-Cre defined neurons results in blunted ventilatory responses under respiratory challenge...
July 6, 2017: Biology Open
https://www.readbyqxmd.com/read/28680103/chemogenetic-silencing-of-gabaergic-dorsal-horn-interneurons-induces-morphine-resistant-spontaneous-nocifensive-behaviours
#10
Keisuke Koga, Kensho Kanehisa, Yuta Kohro, Miho Shiratori-Hayashi, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Hidemasa Furue, Makoto Tsuda
Inhibitory interneurons in the spinal dorsal horn (SDH) are crucial for processing somatosensory information originating in the periphery. However, the effects of the acute and selective inactivation of GABAergic SDH interneurons on pain processing are not fully understood. In this study, we used designer receptors exclusively activated by designer drugs (DREADD) technology and vesicular GABA transporter-Cre (Vgat-Cre) mice to selectively express a modified human muscarinic Gi protein-coupled receptor (hM4Di) in Vgat-Cre (+) GABAergic SDH interneurons in the fourth lumbar segment...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28679672/the-impact-of-the-hepatocyte-to-plasma-ph-gradient-on-the-prediction-of-hepatic-clearance-and-drug-drug-interactions-for-cyp2c9-and-cyp3a4-substrates
#11
Luc Raymond Albert Rougee, Michael A Mohutsky, David W Bedwell, Kenneth J Ruterbories, Stephen D Hall
Surrogate assays for drug metabolism and inhibition are traditionally performed in buffer systems at pH 7.4, despite evidence that hepatocyte intracellular pH is 7.0. This pH gradient can result in a pKa-dependent change in intracellular/extracellular concentrations for ionizable drugs that could affect predictions of clearance and P450 inhibition. The effect of microsomal incubation pH on in vitro enzyme kinetic parameters for CYP2C9 (diclofenac, (S)-warfarin) and CYP3A4 (midazolam, dextromethorphan, testosterone) substrates, enzyme specific reversible inhibitors (amiodarone, desethylamiodarone, clozapine, nicardipine, fluconazole, fluvoxamine, itraconazole) and a mechanism-based inhibitor (amiodarone) was investigated...
July 5, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28677202/dreadd-induced-silencing-of-the-medial-amygdala-reduces-the-preference-for-male-pheromones-and-the-expression-of-lordosis-in-estrous-female-mice
#12
Elizabeth A McCarthy, Arman Maqsudlu, Matthew Bass, Sofia Georghiou, James A Cherry, Michael J Baum
Sexually naïve estrous female mice seek out male urinary pheromones; however, they initially display little receptive (lordosis) behavior in response to male mounts. Vomeronasal - accessory olfactory bulb inputs to the medial amygdala (Me) regulate courtship in female rodents. We used a reversible inhibitory chemogenetic technique (Designer Receptors Exclusively Activated by Designer Drugs; DREADDs) to assess the contribution of Me signaling to females' preference for male pheromones and improvement in receptivity normally seen with repeated testing...
July 5, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28675186/a-successful-re-trial-after-clozapine-myopericarditis
#13
K Sarathy, C Alexopoulos
Clozapine-induced myopericarditis is a well-described adverse drug reaction. Clozapine is also the most efficacious agent in refractory schizophrenia. We report a case of a patient who was successfully re-trialled on clozapine two years after developing myopericarditis, after which multiple lines of alternative treatment failed. We propose a protocol for safely attempting a re-trial of clozapine in such cases.
June 2017: Journal of the Royal College of Physicians of Edinburgh
https://www.readbyqxmd.com/read/28674984/schizophrenia-basic-and-clinical
#14
Joseph T Coyle
Schizophrenia is a chronic severe mental disorder characterized by psychosis, cognitive impairments, and social and motivational deficits. It is associated with a progressive loss of cortical volume after onset of psychosis; nevertheless, cortical atrophy correlates with the cognitive impairments and the negative symptoms but not with the psychosis. The cortical atrophy is not primarily due to neuronal degeneration but rather to neuronal atrophy and loss of glutamatergic synapses. A downregulation of the presynaptic markers for the parvalbumin-expressing GABAergic interneurons that provide recurrent inhibition to cortical pyramidal neurons is another consistent pathologic feature...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28674852/effects-of-long-term-treatment-with-haloperidol-clozapine-and-aripiprazole-on-mice-isolated-vas-deferens
#15
Mehmet Hanifi Tanyeri, Mehmet Emin Buyukokuroglu, Pelin Tanyeri, Oguz Mutlu, Füruzan Yildiz Akar, Güner Ulak, Bekir Faruk Erden
PURPOSE: Sexual dysfunction is a common condition in patients taking antipsychotics and is the most bothersome symptom and adverse drug effect, resulting in a negative effect on treatment compliance. Pharmacology research into human ejeculatory disorders is limited to clinical studies with registered drugs affecting the ejaculation process; therefore, animal research has become the need. We aimed to investigate the effects of haloperidol, clozapine and aripiprazole on serotonin, noradrenaline, adenosine triphosphate (ATP) and potassium chloride (KCl)-induced contractions of the vas deferens in order to evaluate the effect of haloperidol, clozapine and aripiprazole on the contraction of the vas deferens...
July 3, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28673934/activation-of-sf1-neurons-in-the-ventromedial-hypothalamus-by-dreadd-technology-increases-insulin-sensitivity-in-peripheral-tissues
#16
Eulalia A Coutinho, Shiki Okamoto, Ayako Wendy Ishikawa, Shigefumi Yokota, Nobuhiro Wada, Takahiro Hirabayashi, Kumiko Saito, Tatsuya Sato, Kazuyo Takagi, Chen-Chi Wang, Kenta Kobayashi, Yoshihiro Ogawa, Seiji Shioda, Yumiko Yoshimura, Yasuhiko Minokoshi
The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, whereas this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology...
July 3, 2017: Diabetes
https://www.readbyqxmd.com/read/28669537/pneumonia-can-cause-clozapine-intoxication-a-case-report
#17
Can-Jun Ruan, Xue-Yang Zhen, Xin-Liang Ge, Chuan-Yue Wang, Wei Guo, Yi-Lang Tang, Wen-Biao Li, Jose de Leon
No abstract text is available yet for this article.
May 17, 2017: Psychosomatics
https://www.readbyqxmd.com/read/28664926/memory-retention-involves-the-ventrolateral-orbitofrontal-cortex-comparison-with-the-basolateral-amygdala
#18
K S Zimmermann, C Li, D G Rainnie, K J Ressler, S L Gourley
The orbitofrontal cortex (OFC) is thought to link stimuli and actions with anticipated outcomes in order to sustain flexible behavior in an ever-changing environment. How it retains these associations to guide future behavior is less well-defined. Here we focused on one subregion of this heterogeneous structure, the ventrolateral OFC (VLO). CaMKII-driven inhibitory Gi-coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were infused and subsequently activated by their ligand Clozapine-N-oxide (CNO) in conjunction with fear extinction training (a form of aversive conditioning) and response-outcome conditioning (a form of appetitive conditioning)...
June 30, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28664816/cyp2c19-17-protects-against-metabolic-complications-of-clozapine-treatment
#19
Irina Piatkov, Dorgival Caetano, Yolinda Assur, Sue Lynn Lau, Micheline Coelho, Trudi Jones, Tristan Nguyen, Steven Boyages, Mark McLean
OBJECTIVES: Clozapine (CZ) is the most effective drug for managing treatment-resistant schizophrenic disorders. Its use has been limited due to adverse effects, which include weight gain and new-onset diabetes, but the incidence of these varies between patients. METHODS: We investigated 187 Clozapine Clinic patients (of whom 137 consented for genotyping) for the presence of CYP2C19*17 and its association with CZ and NCZ levels, and clinical outcomes. RESULTS: Thirty-nine percent of genotyped patients were carriers of the CYP2C 19*17 polymorphism...
June 30, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28663115/cigarette-smoking-and-schizophrenia-a-specific-clinical-and-therapeutic-profile-results-from-the-face-schizophrenia-cohort
#20
J Mallet, Y Le Strat, F Schürhoff, N Mazer, C Portalier, M Andrianarisoa, B Aouizerate, F Berna, L Brunel, D Capdevielle, I Chereau, T D'Amato, H Denizot, J Dubreucq, C Faget, F Gabayet, P M Llorca, D Misdrahi, R Richieri, R Rey, P Roux, A Schandrin, M Urbach, P Vidailhet, G Fond, C Dubertret, M Andrianarisoa, B Aouizerate, N Bazin, F Berna, O Blanc, L Brunel, E Bulzacka, D Capdevielle, I Chereau-Boudet, G Chesnoy-Servanin, Jm Danion, T D'Amato, A Deloge, C Delorme, H Denizot, J M Dorey, C Dubertret, J Dubreucq, C Faget, C Fluttaz, G Fond, S Fonteneau, F Gabayet, E Giraud-Baro, D Lacelle, C Lançon, H Laouamri, M Leboyer, T Le Gloahec, Y Le Strat, Llorca, J Mallet, E Metairie, D Misdrahi, I Offerlin-Meyer, C Passerieux, P Peri, S Pires, C Portalier, L Ramet, R Rey, C Roman, A Schandrin, F Schürhoff, A Tessier, Am Tronche, M Urbach, F Vaillant, A Vehier, P Vidailhet, E Vilà, H Yazbek, A Zinetti-Bertschy
BACKGROUND: Tobacco use is common in patients with schizophrenia (SZ) but little is known on the role of tobacco in the physiopathology or on the course of the disease. Only few studies embrace an extensive examination of clinical and therapeutic characteristics in stabilized patients. The objective of the present study was to determine the prevalence of tobacco smoking in stabilized SZ outpatients and the clinical and treatment characteristics associated with daily tobacco use in a large community-dwelling sample of patients...
June 27, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
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