1,803 results match your criteria doses second-generation


Second-generation antipsychotics induce cardiotoxicity by disrupting spliceosome signaling: implications from proteomic and transcriptomic analyses.

Pharmacol Res 2021 Jun 4:105714. Epub 2021 Jun 4.

Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University. Shanghai 200032, China. Electronic address:

Second-generation antipsychotics (SGAs) are first-line drugs that are prescribed for mental disorders in clinic. Severe cardiotoxicity has been widely reported and thus limits their clinical application. This study aimed to identify the common mechanism underlying SGAs-induced cardiotoxicity using dual-omics analyses. Read More

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Hormonal contraceptive use in Denmark 2010-2019.

Dan Med J 2021 May 28;68(6). Epub 2021 May 28.

Introduction: Hormonal contraception (HC) celebrates its 60th anniversary this year. Thanks to thousands of scientific studies on these products, we now have solid knowledge about the short- and long-term effects and also the adverse effects of different contraceptive types. The aim of this study was to analyse trends in the use of different types of HC through the latest decade in different age groups of Danish women and to study reasons for any changes. Read More

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Effectiveness and Tolerability of First-Line Afatinib for Advanced EGFR-Mutant Non-Small Cell Lung Cancer in Vietnam.

Asian Pac J Cancer Prev 2021 May 1;22(5):1581-1590. Epub 2021 May 1.

Department of Oncology, Hanoi Medical University, Hanoi, Vietnam.

Background: We aimed to evaluate the effectiveness and tolerability of Afatinib as first-line treatment of advanced epidermal growth factor receptor (EGFR) mutant non small cell lung cancer (NSCLC) in a real-world setting.

Patients And Methods: This is a retrospective study of Vietnamese patients  with advanced EGFR-mutant NSCLC treated with first-line afatinib at the National Cancer Hospital from 1st January 2018 to 31st October 2020. Patients' demographic, clinical and treatment data were captured. Read More

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Pharmacokinetics, pharmacodynamics, and tolerability of subcutaneous administration of a novel glycoprotein IIb/IIIa inhibitor, RUC-4, in patients with ST-segment elevation myocardial infarction.

EuroIntervention 2021 May 18. Epub 2021 May 18.

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands.

Background: Pre-hospital platelet inhibition in patients with ST-segment elevation myocardial infarction (STEMI) may improve outcomes. RUC-4 is a novel, second-generation glycoprotein IIb/IIIa inhibitor designed for first-point-of-medical-contact treatment for STEMI by subcutaneous injection.

Aims: The open-label, phase 2A, CEL-02 trial aimed to assess the pharmacodynamics (PD), pharmacokinetics (PK), and tolerability of RUC-4 in STEMI patients undergoing primary PCI (pPCI). Read More

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A ganglionic blocker and adrenoceptor ligands modify clozapine-induced insulin resistance.

Psychoneuroendocrinology 2021 May 12;129:105257. Epub 2021 May 12.

Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver V6T 1Z3, BC, Canada. Electronic address:

Clozapine is a second generation antipsychotic drug that has proven to be helpful in the management of patients with psychotic disorders that are resistant to other medications. Unfortunately, the majority of patients treated with clozapine develop metabolic dysregulation, including weight gain and insulin resistance. There are few treatments available to effectively counter these side-effects. Read More

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Standard versus reduced dose of antipsychotics for relapse prevention in multi-episode schizophrenia: a systematic review and meta-analysis of randomised controlled trials.

Lancet Psychiatry 2021 Jun;8(6):471-486

Department of Psychiatry, The Zucker Hillside Hospital, New York, NY, USA; Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany. Electronic address:

Background: Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is unclear. We aimed to compare risks and benefits of reduced versus standard doses of antipsychotics.

Methods: We searched Embase, Medline, PsycINFO, and the Cochrane Library from database inception until June 17, 2020, for randomised trials in adults with schizophrenia or schizoaffective disorder lasting at least 24 weeks, including individuals clinically stable at baseline, and comparing at least two doses of the same antipsychotic, excluding trials in first-episode psychosis or treatment-resistant schizophrenia. Read More

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Protracted Hiccups Induced by Aripiprazole and Regressed after Administration of Gabapentin.

Case Rep Psychiatry 2021 22;2021:5567152. Epub 2021 Apr 22.

Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 57, 56100 Pisa, Italy.

Hiccups are sudden, repeated, and involuntary contractions of the diaphragm muscle (myoclonic contraction). It involves a reflex arc that, once activated, causes a strong contraction of the diaphragm immediately followed by the closure of the glottis translating into the classic "hic" sound. Hiccups can be short, persistent, and intractable depending on the duration. Read More

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Clozapine affects the pharmacokinetics of risperidone and inhibits its metabolism and P-glycoprotein-mediated transport in vivo and in vitro: A safety attention to antipsychotic polypharmacy with clozapine and risperidone.

Toxicol Appl Pharmacol 2021 Jul 3;422:115560. Epub 2021 May 3.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, PR China.

Antipsychotic polypharmacy (APP), as one maintenance treatment strategy in patients with schizophrenia, has gained popularity in real-world clinical settings. Risperidone (RIS) and clozapine (CLZ) are the most commonly prescribed second-generation antipsychotics, and they are often used in combination as APP. In this study, the pharmacokinetics of RIS and CLZ in rats were examined after co-administration to explore the reliability and rationality of co-medication with RIS and CLZ. Read More

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Antihistamines Modulate Functional Activity of Macrophages.

Bull Exp Biol Med 2021 Apr 24;170(6):759-762. Epub 2021 Apr 24.

Pacific State Medical University, Ministry of Health of the Russian Federation, Vladivostok, Russia.

We compared the effects of the first-, second- and third-generation antihistamines in different doses on enzyme activity and cytokine production by macrophages and their death using an in vitro model. It was found that decreasing the dose led to an increase in the number of viable cells; after contact with second-generation antihistamines (loratadine, desloratadine), apoptosis of macrophages predominated. A dose-dependent increase in activity of ATPase and 5'-AMP with less pronounced effect of second-generation drugs was revealed. Read More

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The Use of Bruton's Tyrosine Kinase Inhibitors to Treat Allergic Disorders.

Curr Treat Options Allergy 2021 Apr 16:1-13. Epub 2021 Apr 16.

Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD USA.

Purpose Of Review: Studies show that inhibitors of Bruton's tyrosine kinase (BTKis), currently FDA-approved for the treatment of B cell malignancies, can prevent IgE-mediated reactions through broad inhibition of the FcεRI signaling pathway in human mast cells and basophils. This review will summarize recent data supporting the use of these drugs as novel therapies in various allergic disorders.

Recent Findings: Recent studies have shown that BTKis can prevent IgE-mediated degranulation and cytokine production in primary human mast cells and basophils. Read More

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Trial of Psilocybin versus Escitalopram for Depression.

N Engl J Med 2021 04;384(15):1402-1411

From the Centre for Psychedelic Research, Department of Brain Sciences, Faculty of Medicine, Imperial College London, London.

Background: Psilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking.

Methods: In a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, a selective serotonin-reuptake inhibitor, over a 6-week period. Patients were assigned in a 1:1 ratio to receive two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo (psilocybin group) or two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram (escitalopram group); all the patients received psychological support. Read More

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Insulin doses requirements in patients with type 1 diabetes using glargine U300 or degludec in routine clinical practice.

J Investig Med 2021 Jun 26;69(5):983-988. Epub 2021 Mar 26.

Endocrinology and Nutrition, University Hospital of Puerto Real, Puerto Real, Andalucía, Spain.

There are not many real-world studies evaluating daily insulin doses requirements (DIDR) in patients with type 1 diabetes (T1D) using second-generation basal insulin analogs, and such comparison is necessary. The aim of this study was to compare DIDR in individuals with T1D using glargine 300 UI/mL (IGlar-300) or degludec (IDeg) in real clinical practice. An observational, retrospective study was designed in 412 patients with T1D (males: 52%; median age 37. Read More

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Radiation exposure and establishment of diagnostic reference levels of whole-body low-dose CT for the assessment of multiple myeloma with second- and third-generation dual-source CT.

Acta Radiol 2021 Mar 20:2841851211003287. Epub 2021 Mar 20.

Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany.

Background: In the assessment of diseases causing skeletal lesions such as multiple myeloma (MM), whole-body low-dose computed tomography (WBLDCT) is a sensitive diagnostic imaging modality, which has the potential to replace the conventional radiographic survey.

Purpose: To optimize radiation protection and examine radiation exposure, and effective and organ doses of WBLDCT using different modern dual-source CT (DSCT) devices, and to establish local diagnostic reference levels (DRL).

Material And Methods: In this retrospective study, 281 WBLDCT scans of 232 patients performed between January 2017 and April 2020 either on a second- (A) or third-generation (B) DSCT device could be included. Read More

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Sub-lethal aquatic doses of pyriproxyfen may increase pyrethroid resistance in malaria mosquitoes.

PLoS One 2021 18;16(3):e0248538. Epub 2021 Mar 18.

Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.

Background: Pyriproxyfen (PPF), an insect growth hormone mimic is widely used as a larvicide and in some second-generation bed nets, where it is combined with pyrethroids to improve impact. It has also been evaluated as a candidate for auto-dissemination by adult mosquitoes to control Aedes and Anopheles species. We examined whether PPF added to larval habitats of pyrethroid-resistant malaria vectors can modulate levels of resistance among emergent adult mosquitoes. Read More

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The offspring of alcohol-exposed sires exhibit heightened ethanol intake and behavioral alterations in the elevated plus maze.

Alcohol 2021 May 13;92:65-72. Epub 2021 Mar 13.

Southern Connecticut State University, 501 Crescent St., New Haven, CT, 06515, United States.

Research suggests that addictive traits are indeed heritable, but very few preclinical studies have explored transgenerational effects of paternal alcohol exposure. The present study addressed this gap in knowledge. We explored whether offspring of ethanol-exposed sires would be more likely to accept ethanol than descendants of water-exposed and control sires. Read More

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A Phase II Study to Assess the Efficacy of Osimertinib in Patients With EGFR Mutation-positive NSCLC Who Developed Isolated CNS Progression (T790M-negative or Unknown) During First- or Second-generation EGFR-TKI or Systemic Disease Progression (T790M-negative) After Treatment With First- or Second-generation EGFR-TKI and Platinum-based Chemotherapy (WJOG12819L).

Clin Lung Cancer 2021 Jan 25. Epub 2021 Jan 25.

Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has recently been established as a standard treatment option for chemotherapy-naive patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC). However, only about one-half of patients who have received prior treatment with a first- or second-generation EGFR-TKI are eligible for osimertinib therapy because its indication in the second-line setting is limited to metastatic NSCLC positive for the T790M resistance mutation of EGFR. The dose-escalation part of a study in which patients received osimertinib at doses of 20 to 240 mg once daily after the development of resistance to first- or second-generation EGFR-TKIs revealed a response rate of 21% and a median progression-free survival of 2. Read More

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January 2021

Ameliorative effects of astaxanthin on brain tissues of alzheimer's disease-like model: cross talk between neuronal-specific microRNA-124 and related pathways.

Mol Cell Biochem 2021 May 11;476(5):2233-2249. Epub 2021 Feb 11.

Biochemistry Department, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, EL-Hadara, POB: 21561, Alexandria, Egypt.

Alzheimer's disease (AD) is a chronic, progressive, multifactorial, and the most common neurodegenerative disease which causes dementia and mental deterioration in the elderly. The available treatments for AD are not disease-modifying drugs and only provide symptomatic relief. Astaxanthin (ATX), a second-generation antioxidant, is a dark red carotenoid and exhibits the highest antioxidant capacity, anti-inflammatory, neuroprotective, and antiapoptotic effects. Read More

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Zolpidem in treatment resistant adolescent catatonia: a case series.

Scand J Child Adolesc Psychiatr Psychol 2020 15;8:135-138. Epub 2020 Sep 15.

Department of Psychiatry, Institute of Human Behaviour and Allied Sciences, Delhi, India.

Catatonia is a well-established psycho-motor disorder occurring in the background of various psychiatric and medical disorders. Catatonia is commonly associated with psychiatric disorders, especially affective disorders followed by schizophrenia. However, almost 20% occur in the background of different medical and neurological disorders which need to be properly examined and investigated. Read More

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September 2020

Short- and long-term exposures of the synthetic cannabinoid 5F-APINAC induce metabolomic alterations associated with neurotransmitter systems and embryotoxicity confirmed by teratogenicity in zebrafish.

Comp Biochem Physiol C Toxicol Pharmacol 2021 May 6;243:109000. Epub 2021 Feb 6.

Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia. Electronic address:

Introduction: Synthetic cannabinoids are abused substances with strong psychoactive effects. Little is known about the effects on neurotransmission and the toxicity of the second-generation cannabinoid 5F-APINAC. The objective was to assess the influence of short- and long-term exposures of 5F-APINAC on metabolites associated with neurotransmission on zebrafish. Read More

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Preventive and Therapeutic Efficacy of ONO-4641, a Selective Agonist for Sphingosine 1-Phosphate Receptor 1 and 5, in Preclinical Models of Type 1 Diabetes Mellitus.

Biol Pharm Bull 2021 ;44(2):188-196

Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd.

ONO-4641, 1-({6-[(2-methoxy-4-propylbenzyl)oxy]-1-methyl-3,4-dihydronaphthalen-2-yl}methyl)azetidine-3-carboxylic acid (ceralifimod), is a second-generation sphingosine 1-phosphate receptor agonist selective for sphingosine 1-phosphate receptors 1 and 5, and has clinical effects in multiple sclerosis. The objective of the present study was to explore other potential indications for ONO-4641 based on its immunomodulatory effects. ONO-4641 was tested in non-obese diabetic (NOD) mice, an animal model of spontaneous type 1 diabetes mellitus, an autoimmune disease with unmet medical needs. Read More

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January 2021

Prescribing pattern of antipsychotic medication for first-episode psychosis: a retrospective cohort study.

BMJ Open 2021 01 31;11(1):e040387. Epub 2021 Jan 31.

School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.

Objective: Guidelines for antipsychotic use in first-episode psychosis (FEP) recommend that medication be chosen initially on the basis of side effect profile with doses at the lower end of the range. Our objective was to describe the pattern of antipsychotic use in FEP over a period of 21 years in the context of changing clinical guidelines and the development of specialist early intervention in psychosis (EIP) services.

Setting: A community-based mental health service in South County Dublin (population 187 000) and a large private hospital. Read More

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January 2021

Revisiting a lower starting dose of alectinib in ALK-Positive non-small cell lung cancer.

Cancer Treat Res Commun 2021 23;27:100319. Epub 2021 Jan 23.

Division of Hematology, Department of Medicine, Philippine General Hospital and University of the Philippines Manila, Taft Avenue, Manila, 1000 Philippines.

We present here a case of ALK-positive lung adenocarcinoma that has been started on Alectinib. Treatment has been initiated at the recommended initial dose, but it subsequently required a dose adjustment following adverse drug events. Alectinib is a second-generation, CNS-active, tyrosine kinase inhibitor used in the treatment of ALK-positive non-small cell lung cancer. Read More

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January 2021

A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models.

PLoS One 2021 28;16(1):e0246211. Epub 2021 Jan 28.

Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, Canada.

Background: The second generation antipsychotic drugs represent the most common form of pharmacotherapy for schizophrenia disorders. It is now well established that most of the second generation drugs cause metabolic side-effects. Risperidone and its active metabolite paliperidone (9-hydroxyrisperidone) are two commonly used antipsychotic drugs with moderate metabolic liability. Read More

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January 2021

Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock Model.

Int J Mol Sci 2021 Jan 21;22(3). Epub 2021 Jan 21.

Independent Unit of Experimental Neuropathophysiology, Medical University of Lublin, Jaczewskiego 8b, PL-20-090 Lublin, Poland.

Accumulating experimental studies show that antiarrhythmic and antiepileptic drugs share some molecular mechanisms of action and can interact with each other. In this study, the influence of amiodarone (a class III antiarrhythmic drug) on the antiseizure action of four second-generation antiepileptic drugs was evaluated in the maximal electroshock model in mice. Amiodarone, although ineffective in the electroconvulsive threshold test, significantly potentiated the antielectroshock activity of oxcarbazepine and pregabalin. Read More

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January 2021

Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice.

Pharmacol Rep 2021 Apr 25;73(2):516-524. Epub 2021 Jan 25.

Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, PL-20-954, Lublin, Poland.

Background: Due to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the antielectroshock action of phenytoin and valproate in mice.

Materials And Methods: As a continuation of previous experiments, we examined the effect of sotalol on the action of four chosen second-generation antiepileptic drugs (oxcarbazepine, lamotrigine, pregabalin, and topiramate) against the maximal electroshock in mice. Read More

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Toxicokinetics of the tumour cell mitochondrial toxin, PENAO, in rodents.

Authors:
Philip J Hogg

Invest New Drugs 2021 Jun 19;39(3):756-763. Epub 2021 Jan 19.

The Centenary Institute, Camperdown, NSW, 2050, Australia.

PENAO (4-(N-(S-penicillaminylacetyl)amino)phenylarsonous acid) is a second-generation peptide arsenical that inactivates mitochondria in proliferating tumour cells by covalently reacting with mitochondrial inner-membrane adenine nucleotide transferase. The toxicokinetics of PENAO has been investigated in Sprague-Dawley rats to inform route of administration and dosing for human clinical trials. PENAO was well tolerated at 3. Read More

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Factors associated with laxative use in schizophrenia patients treated with second-generation antipsychotics.

Eur Neuropsychopharmacol 2021 Feb 6;43:139-146. Epub 2021 Jan 6.

Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.

The aim of this study was to investigate factors associated with concomitant laxative use among schizophrenia patients discharged on second-generation antipsychotics (SGAs) at two large psychiatric hospitals in Taiwan. Patients with schizophrenia who were discharged between 2006 and 2017 and received SGA monotherapy at discharge were included in the analysis. Multivariate logistic regression was used to identify factors associated with regular laxative use at discharge. Read More

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February 2021

A Novel Second-Generation EP2 Receptor Antagonist Reduces Neuroinflammation and Gliosis After Status Epilepticus in Rats.

Neurotherapeutics 2021 Jan 6. Epub 2021 Jan 6.

Department of Pharmacology and Chemical Biology, Emory University, 1510 Clifton Road NE, Atlanta, GA, 30322, USA.

Prostaglandin-E (PGE), an important mediator of inflammation, achieves its functions via four different G protein-coupled receptors (EP1, EP2, EP3, and EP4). We previously demonstrated that the EP2 receptor plays a proinflammatory and neurodegenerative role after status epilepticus (SE). We recently developed TG8-260 as a second-generation highly potent and selective EP2 antagonist. Read More

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January 2021

Effects of JL13, a pyridobenzoxazepine compound, in dopaminergic and glutamatergic models of antipsychotic activity.

Behav Pharmacol 2021 Feb;32(1):2-8

Department of Pharmacology, Institute of Biological Sciences.

The pyridobenzoxazepine compound, 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine (JL13), has been developed as a potential antipsychotic drug. We tested the hypothesis that JL13 is efficacious in both dopaminergic and glutamatergic animal models of schizophrenia. We investigated JL13 for its efficacy to prevent cocaine- and ketamine-induced hyperlocomotion and MK-801-induced deficits in prepulse inhibition (PPI) of the startle reflex. Read More

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February 2021

Preclinical optimization of Ly6E-targeted ADCs for increased durability and efficacy of anti-tumor response.

MAbs 2021 Jan-Dec;13(1):1862452

Antibody Engineering, Genentech Inc , South San Francisco, CA, USA.

Early success with brentuximab vedotin in treating classical Hodgkin lymphoma spurred an influx of at least 20 monomethyl auristatin E (MMAE) antibody-drug conjugates (ADCs) into clinical trials. While three MMAE-ADCs have been approved, most of these conjugates are no longer being investigated in clinical trials. Some auristatin conjugates show limited or no efficacy at tolerated doses, but even for drugs driving initial remissions, tumor regrowth and metastasis often rapidly occur. Read More

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December 2020