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Loxapine

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https://www.readbyqxmd.com/read/29106549/the-in-vitro-actions-of-loxapine-on-dopaminergic-and-serotonergic-receptors-time-to-consider-atypical-classification-of-this-antipsychotic-drug
#1
Florian Ferreri, Dominique Drapier, Emmanuelle Baloche, Mehemed Ouzid, Luc Zimmer, Pierre-Michel Llorca
Background: The denomination of typical antipsychotic for loxapine has poor relation to current knowledge of the molecule's relevant modes of action. Method: Competition binding experiments were performed on expressed human recombinant receptors in CHO cells and HEK-293 cells for D1 to D5, 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro autoradiographies using [ 11C]-Raclopride [18F]-Altanserin [18F]-MPPF [11C]-SB207145 and [18F]-2FNQ1P were measured in brain tissue of a male primate followed by addition of increasing doses of loxapine succinate...
November 2, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29045249/inhaled-loxapine-for-agitation-in-intoxicated-patients-a-case-series
#2
Carlos Roncero, Elena Ros-Cucurull, Raúl Felipe Palma-Álvarez, Alfonso Carlos Abad, Christian Fadeuilhe, Miquel Casas, Lara Grau-López
OBJECTIVES: Episodes of agitation are frequent in intoxicated patients who have a substance use disorder, a psychiatric disorder or both (dual diagnosis). For managing the agitation, it is necessary to act promptly in a safe environment and addressing any underlying etiology. Inhaled loxapine improves symptoms of agitation in adults with psychiatric disorders (eg, schizophrenia) within 10 minutes of administration. Recently, some reports have documented the usefulness of loxapine in dual diagnoses patients with agitation...
November 2017: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/28962597/periodic-catatonia-with-long-term-treatment-a-case-report
#3
Ruei-An Chen, Tiao-Lai Huang
BACKGROUND: Periodic catatonia has long been a challenging diagnosis and there are no absolute guidelines for treatment when precipitating factors are also unclear. We report a schizophrenia patient with periodic catatonia with a 15-year treatment course. A possible correlation between decreased daylight exposure and periodic attacks has been observed. CASE PRESENTATION: We describe a 49-year-old woman with periodic catatonia associated with schizophrenia with 15 years of follow-up...
September 29, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28933260/older-and-newer-strategies-for-the-pharmacological-treatment-of-agitation-in-schizophrenia-and-bipolar-disorder
#4
Giovanni Amodeo, Andrea Fagiolini, Gabriele Sachs, Andreas Erfurth
BACKGROUND: Treatment of acute agitation in patients with bipolar disorder and schizophrenia is a multifaceted and dynamic task, which presents unique and complex challenges to healthcare providers. OBJECTIVE: To ascertain and describe which medications are best to use in agitated patients with schizophrenia or bipolar disorder Method: Selective review of current guidelines and of the literature pertaining to the treatment of agitation in patients with schizophrenia or bipolar disorder Results: Pharmacologic treatment of agitation should be based on an assessment of the most likely cause of the agitation...
September 18, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28877705/loxapine-to-control-agitation-during-weaning-from-mechanical-ventilation
#5
Stéphane Gaudry, Benjamin Sztrymf, Romain Sonneville, Bruno Megarbane, Guillaume Van Der Meersch, Dominique Vodovar, Yves Cohen, Jean-Damien Ricard, David Hajage, Laurence Salomon, Didier Dreyfuss
BACKGROUND: Weaning from mechanical ventilation (MV) may be impeded by the occurrence of agitation. Loxapine has the ability to control agitation without affecting spontaneous ventilation. The aim of this study was to establish whether loxapine would reduce MV weaning duration in agitated patients. METHODS: We performed a multicentre, double-blind, placebo-controlled, parallel group, randomised trial. Patients who were potential candidates for weaning but exhibited agitation (Richmond Agitation-Sedation Scale score ≥ 2) after sedation withdrawal were randomly assigned to receive either loxapine or placebo...
September 6, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28803208/n-glucuronidation-catalyzed-by-ugt1a4-and-ugt2b10-in-human-liver-microsomes-assay-optimization-and-substrate-identification
#6
Danyi Lu, Qian Xie, Baojian Wu
N-glucuronidation is an important pathway for metabolism and disposition of tertiary amines in humans. This reaction is mainly catalyzed by the enzymes UGT1A4 and UGT2B10. However, the metabolic patterns of UGT1A4- and UGT2B10-mediated N-glucuronidation are not fully clear. In this study, we first optimized in vitro reaction conditions for N-glucuronidation by using specific substrates (i.e., trifluoperazine for UGT1A4, cotinine and amitriptyline for UGT2B10). Furthermore, we found that hepatic N-glucuronidation showed significant species differences...
October 25, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28755876/a-computational-network-analysis-based-on-targets-of-antipsychotic-agents
#7
Lei Gao, Shuo Feng, Zhao-Yuan Liu, Jiu-Qiang Wang, Ke-Ke Qi, Kai Wang
Currently, numerous antipsychotic agents have been developed in the area of pharmacological treatment of schizophrenia. However, the molecular mechanism underlying multi targets of antipsychotics were yet to be explored. In this study we performed a computational network analysis based on targets of antipsychotic agents. We retrieved a total of 96 targets from 56 antipsychotic agents. By expression enrichment analysis, we identified that the expressions of antipsychotic target genes were significantly enriched in liver, brain, blood and corpus striatum...
July 26, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28721057/safety-tolerability-and-risks-associated-with-first-and-second-generation-antipsychotics-a-state-of-the-art-clinical-review
#8
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/28647110/success-of-tardive-electroconvulsive-therapy-sessions-after-loxapine-induced-malignant-syndrome-in-the-context-of-very-poor-metabolisation
#9
Juliette Descoeur, Laurent Philibert, Kevin Chalard, Jérôme Attal, Pierre Petit, Kada Klouche, Mathieu Olivier
We report the success of tardive electroconvulsive therapy in a case of loxapine malignant syndrome with catatonia. Loxapine and its metabolites were measured in biological samples by liquid chromatography coupled to tandem mass spectrometry. Genes were studied by sequencing and quantitative polymerase chain reaction (PCR). Plasmatic drug concentrations showed a supratherapeutic concentration of loxapine with a very low 8-hydroxyloxapine/loxapine ratio (range from 0.32 to 0.66, normal value>2 for 100mg) and a very long elimination half-life of loxapine (half-life>140h, normal value from 1 to 4hours)...
May 29, 2017: Thérapie
https://www.readbyqxmd.com/read/28510296/pharmacokinetics-and-safety-of-single-dose-inhaled-loxapine-in-children-and-adolescents
#10
Sally Selim, Robert Riesenberg, James Cassella, Jeevan Kunta, Edward Hellriegel, Mark A Smith, Alexander A Vinks, Laura Rabinovich-Guilatt
This multisite open-label study sought to characterize the pharmacokinetics and safety of a single dose of inhaled loxapine in children and adolescents. Loxapine powder for oral inhalation was administered via a single-use handheld drug device to children and adolescents (aged 10-17 years) with any condition warranting chronic antipsychotic use. Patients were dosed according to body weight and cohort (<50 kg [n = 15], 2.5 or 5 mg; ≥50 kg [n = 15], 5 or 10 mg); the first 6 patients (cohort 1) enrolled in each weight group received the lower dose...
May 16, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28488314/pharmacist-intervention-to-detect-drug-adverse-events-on-admission-to-the-emergency-department-two-case-reports-of-neuroleptic-malignant-syndrome
#11
F Leenhardt, D Perier, V Pinzani, I Giraud, M Villiet, A Castet-Nicolas, V Gourhant, C Breuker
WHAT IS KNOWN AND OBJECTIVE: Neuroleptic malignant syndrome (NMS) is a rare but severe adverse effect of antipsychotic drugs. CASE DESCRIPTION: We report two cases of NMS highlighted by clinical pharmacists in an emergency unit during summer. One of them was fatal. Medication reconciliation processes performed at admission identified treatment with loxapine for one of them and with loxapine and clozapine for the other. Interview of the patients highlighted clinical symptoms suggesting NMS, allowing the pharmacists to alert the medical team...
August 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28376877/rationale-and-design-of-the-placid-study-a-randomised-trial-comparing-the-efficacy-and-safety-of-inhaled-loxapine-versus-im-aripiprazole-in-acutely-agitated-patients-with-schizophrenia-or-bipolar-disorder
#12
RANDOMIZED CONTROLLED TRIAL
L San, G Estrada, N Oudovenko, E Vieta
BACKGROUND: The management of acute agitation manifesting in patients with schizophrenia or bipolar disorder requires swift pharmacological intervention to provide rapid symptomatic relief and prevent escalation to aggression and violence. Antipsychotic medications are widely used in this setting and the availability of an inhaled formulation with deep lung absorption of the antipsychotic loxapine has the potential to deliver a faster onset of therapeutic effect than the available intramuscular formulations of antipsychotics...
April 4, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28366665/the-phe932ile-mutation-in-kcnt1-channels-associated-with-severe-epilepsy-delayed-myelination-and-leukoencephalopathy-produces-a-loss-of-function-channel-phenotype
#13
Katherine M Evely, Kerri D Pryce, Arin Bhattacharjee
Sodium-activated potassium (KNa) channels contribute to firing frequency adaptation and slow after hyperpolarization. The KCNT1 gene (also known as SLACK) encodes a KNa subunit that is expressed throughout the central and peripheral nervous systems. Missense mutations of the SLACK C-terminus have been reported in several patients with rare forms of early onset epilepsy and in some cases severely delayed myelination. To date, such mutations identified in patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), epilepsy of infancy with migrating focal seizures (EIMFS) and Ohtahara syndrome (OS) have been reported to be gain-of-function mutations (Villa and Combi, 2016)...
May 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/28335658/dopamine-antagonists-for-treatment-resistance-in-autism-spectrum-disorders-review-and-focus-on-bdnf-stimulators-loxapine-and-amitriptyline
#14
REVIEW
Jessica A Hellings, L Eugene Arnold, Joan C Han
Drug development and repurposing are urgently needed for individuals with autism spectrum disorders (ASD) and psychiatric comorbidity, which often presents as aggression and self-injury. Areas covered: We review dopamine antagonists, including classical and atypical, as well as unconventional antipsychotics in ASD. The older antipsychotic loxapine is discussed in terms of preliminary albeit limited evidence in ASD. Emerging promise of amitriptyline in ASD is discussed, together with promising BDNF effects of loxapine and amitriptyline...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28208695/the-role-of-inhaled-loxapine-in-the-treatment-of-acute-agitation-in-patients-with-psychiatric-disorders-a-clinical-review
#15
REVIEW
Domenico de Berardis, Michele Fornaro, Laura Orsolini, Felice Iasevoli, Carmine Tomasetti, Andrea de Bartolomeis, Nicola Serroni, Alessandro Valchera, Alessandro Carano, Federica Vellante, Stefano Marini, Monica Piersanti, Giampaolo Perna, Giovanni Martinotti, Massimo Di Giannantonio
Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28205038/clinical-trial-simulations-and-pharmacometric-analysis-in-pediatrics-application-to-inhaled-loxapine-in-children-and-adolescents
#16
Min Dong, Tsuyoshi Fukuda, Sally Selim, Mark A Smith, Laura Rabinovich-Guilatt, James V Cassella, Alexander A Vinks
BACKGROUND AND OBJECTIVES: Loxapine for inhalation is a drug-device combination product approved in adults for the acute treatment of agitation associated with schizophrenia or bipolar I disorder. The primary objective of this study was to develop a clinical trial protocol to support a phase I pharmacokinetic study in children aged 10 years and older. In addition, this report details the results of the clinical study in relation to the predicted likelihood of achieving the target exposure associated with therapeutic effect in adults...
February 15, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28187007/clinicaltrials-gov-inhaled-loxapine-and-safety-issues
#17
Richard I Shader
No abstract text is available yet for this article.
April 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28152454/simultaneous-quantification-of-loxapine-loxapine-n-oxide-amoxapine-8-hydroxyloxapine-and-7-hydroxyloxapine-in-human-plasma-using-lc-ms-ms
#18
MULTICENTER STUDY
Min Meng, Nan Zhao, Carrie C Pederson, Edward Harrison, Charisse Green, Steven H Gorman, Scott Reuschel
Loxapine is an antipsychotic medication used for the treatment of schizophrenia. In vivo, loxapine is metabolized to multiple metabolites. A high performance liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of loxapine and 4 of its metabolites, loxapine N-oxide, amoxapine (N-desmethyl loxapine), 8-hydroxyloxapine and 7-hydroxyloxapine, in human plasma to support regulated clinical development. During method development, several technical challenges such as poor chromatography, separation of structural isomers, and inadequate sensitivity were met and overcome...
March 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27980039/intracellular-calcium-mobilization-in-response-to-ion-channel-regulators-via-a-calcium-induced-calcium-release-mechanism
#19
Terry Petrou, Hervør L Olsen, Christopher Thrasivoulou, John R Masters, Jonathan F Ashmore, Aamir Ahmed
Free intracellular calcium ([Ca(2+)]i), in addition to being an important second messenger, is a key regulator of many cellular processes including cell membrane potential, proliferation, and apoptosis. In many cases, the mobilization of [Ca(2+)]i is controlled by intracellular store activation and calcium influx. We have investigated the effect of several ion channel modulators, which have been used to treat a range of human diseases, on [Ca(2+)]i release, by ratiometric calcium imaging. We show that six such modulators [amiodarone (Ami), dofetilide, furosemide (Fur), minoxidil (Min), loxapine (Lox), and Nicorandil] initiate release of [Ca(2+)]i in prostate and breast cancer cell lines, PC3 and MCF7, respectively...
February 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27637870/-quetiapine-and-anticholinergic-drugs-induced-ischaemic-colitis-a-case-study
#20
REVIEW
P Cuny, M Houot, S Ginisty, S Horowicz, F Plassart, H Mentec, P Eftekhari
INTRODUCTION: The aim of this paper is to underline the need for systematic monitoring of patients treated with anticholinergic antipsychotic drugs. We present the clinical history of a 34-year-old adult, treated with quetiapine in combination with other drugs with anticholinergic effects. CASE REPORT: A 34-year-old male adult had been suffering from bipolar disorder since 2001. He was treated with risperidone, but he was not compliant due to adverse effects, including decreased libido and erectile dysfunction...
February 2017: L'Encéphale
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