Search results for: Morten Laursen

Items from 1 to 13 out of 13 results

article

A small molecule activator of Na_v1.1 channels increases fast‐spiking interneuron excitability and GABAergic transmission in vitro and has anti‐convulsive effects in vivo

Kristen Frederiksen, Dunguo Lu, Jinhui Yang, Henrik Sindal Jensen, more

European Journal of Neuroscience > 46 > 3 > 1887 - 1896

Na_v1.1 (SCN1A) channels primarily located in gamma‐aminobutyric acid (GABA)ergic fast‐spiking interneurons are pivotal for action potential generation and propagation in these neurons. Inappropriate function of fast‐spiking interneurons, leading to disinhibition of pyramidal cells and network desynchronization, correlates with decreased cognitive capability. Further, reduced functionality of Na_v1...

article

Novel selective PDE type 1 inhibitors cause vasodilatation and lower blood pressure in rats

Morten Laursen, Lilliana Beck, Jan Kehler, Claus Tornby Christoffersen, more

British Journal of Pharmacology > 174 > 15 > 2563 - 2575

Background and Purpose The PDE enzymes (PDE1–11) hydrolyse and thus inactivate cyclic nucleotides and are important in the regulation of the cardiovascular system. Here,we have investigated the effects on the cardiovascular system, of two novel selective PDE1 inhibitors, Lu AF41228 and Lu AF58027. Experimental Approach We used rat mesenteric small arteries (internal diameters of 200–300 μm), RT‐PCR...

article

Ion currents of cardiomyocytes in different regions of the Göttingen minipig heart

Per Arlock, Tomas Mow, Trygve Sjöberg, Anders Arner, more

Journal of Pharmacological and Toxicological Methods > 2017 > 86 > C > 12-18

The Göttingen minipig is a promising model for pharmacological safety assessment and for translational research in cardiology. We have examined the main ion currents in cardiomyocytes of the minipig heart.Cardiac cells were isolated from different cardiac regions (endo-, mid- and epicardial left ventricle and right ventricle) from Göttingen minipigs and examined using the whole cell patch clamp technique...

article

Exploratory toxicology as an integrated part of drug discovery. Part II: Screening strategies

Jorrit J. Hornberg, Morten Laursen, Nina Brenden, Mikael Persson, more

Drug Discovery Today > 2014 > 19 > 8 > 1137-1144

In an effort to reduce toxicity-related attrition, different strategies have been implemented throughout the pharmaceutical industry. Previously (in Part I), we have outlined our ‘integrated toxicology’ strategy, which aims to provide timely go/no-go decisions (fail early) but also to show a direction to the drug discovery teams (showing what will not fail). In this review (Part II of the series)...

article

Exploratory toxicology as an integrated part of drug discovery. Part I: Why and how

Jorrit J. Hornberg, Morten Laursen, Nina Brenden, Mikael Persson, more

Drug Discovery Today > 2014 > 19 > 8 > 1131-1136

Toxicity and clinical safety have major impact on drug development success. Moving toxicological studies into earlier phases of the R&D chain prevents drug candidates with a safety risk from entering clinical development. However, to identify candidates without such risk, safety has to be designed actively. Therefore, we argue that toxicology should be fully integrated into the discovery process...

article

Discovery and optimization of Lu AF58801, a novel, selective and brain penetrant positive allosteric modulator of alpha-7 nicotinic acetylcholine receptors: Attenuation of subchronic phencyclidine (PCP)-induced cognitive deficits in rats following oral administration

Jørgen Eskildsen, John P. Redrobe, Anette G. Sams, Kim Dekermendjian, more

Bioorganic & Medicinal Chemistry Letters > 2014 > 24 > 1 > 288-293

In this Letter, we describe a chemical lead optimization campaign starting from a novel, weak α7 nicotinic acetylcholine receptor positive allosteric modulator (PAM) hit from a HTS screen. Exploration of the structure–activity relationships for α7 PAM potency, intrinsic hepatic clearance, the structure–property relationships for lipophilicity, and thermodynamic solubility, led to the identification...

article

3-Model characterization of the relation between cardiac repolarization and temperature in guinea pig

Morten Laursen, Anders B. Lassen, Olle Åkerlund, Rikke B. Strange Hansen, more

Journal of Pharmacological and Toxicological Methods > 2012 > 66 > 2 > 175

article

Keeping the rhythm — Pro-arrhythmic investigations in isolated Göttingen minipig hearts

Morten Laursen, Morten Grunnet, Søren-Peter Olesen, Thomas Jespersen, more

Journal of Pharmacological and Toxicological Methods > 2011 > 64 > 2 > 134-144

Cardiac arrhythmia is a potentially lethal condition. A better prediction and mechanistic understanding of human cardiac arrhythmia is dependent on the development of good animal models. Minipigs are increasingly being used in cardiovascular research and we hypothesize that Langendorff-perfused minipig hearts could serve as a novel model of pro-arrhythmia.We studied arrhythmic biomarkers and overt...

article

Characterization of cardiac repolarization in the Göttingen minipig

Morten Laursen, Søren-Peter Olesen, Morten Grunnet, Tomas Mow, more

Journal of Pharmacological and Toxicological Methods > 2011 > 63 > 2 > 186-195

The minipig represents an attractive experimental animal within cardiovascular research due to its extensive similarities to the human heart in terms of anatomy and physiology. Although minipigs have been used for cardiovascular research for decades no thorough characterization of the minipig cardiac electrophysiology has been performed. Therefore, we have for the first time characterized the minipig...

article

Relation between the QT interval and temperature in Göttingen minipigs: A point to consider

Morten Laursen, Olle Kerlund, Tomas Mow

Journal of Pharmacological and Toxicological Methods > 2010 > 62 > 2 > e11

article

Major ion currents except ito are present in the ventricle of the Göttingen minipig heart

Tomas Mow, Per Arlock, Morten Laursen, Niels-Christian Ganderup

Journal of Pharmacological and Toxicological Methods > 2008 > 58 > 2 > 165

article

Fault diagnosis of a water for injection system using enhanced structural isolation

Morten Laursen, Mogens Blanke, Dilek Düştegör

International Journal of Applied Mathematics and Computer Science > 2008 > 18 > 4 > 593-603

A water for injection system supplies chilled sterile water as a solvent for pharmaceutical products. There are ultimate requirements for the quality of the sterile water, and the consequence of a fault in temperature or in flow control within the process may cause a loss of one or more batches of the production. Early diagnosis of faults is hence of considerable interest for this process. This study...

chapter

Model-checking real-time control programs: verifying LEGO MINDSTORMS^TM systems using UPPAAL

Torsten K. Iversen, Kare J. Kristoffersen, Kim G. Larsen, Morten Laursen, more

Proceedings 12th Euromicro Conference on Real-Time Systems. Euromicro RTS 2000 > 147 - 155

Proceedings 12th Euromicro Conference on Real-Time Systems. Euromicro RTS 2000

The authors present a method for automatic verification of real time control programs running on LEGO(R) RCX^TM bricks using the verification tool UPPAAL. The control programs, consisting of a number of tasks running concurrently, are automatically translated into the timed automata model of UPPAAL. The fixed scheduling algorithm used by the LEGO(R) RCX^TM processor is modeled in UPPAAL, and supply...

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GÖTTINGEN MINIPIG (3)
ACTION POTENTIAL (2)
ECG (2)
ACTIVATORS (1)
ARRHYTHMIA (1)
AUTOMATA THEORY (1)
AUTOMATIC VERIFICATION (1)
CARDIAC (1)
CARDIAC ELECTROPHYSIOLOGY (1)
CONCURRENT TASKS (1)
CONTROL ENGINEERING COMPUTING (1)
CONTROL PROGRAMS (1)
DELAYED RECTIFIER K+ CHANNEL (1)
ELECTROPHYSIOLOGY (1)
FAULT DIAGNOSIS (1)
FAULT ISOLATION (1)
FIXED SCHEDULING ALGORITHM (1)
HEART (1)
HERG (1)
INTERNEURONS (1)
INWARD RECTIFIER K+ CHANNEL (1)
ION CHANNEL (1)
L-TYPE CA2+ CHANNEL (1)
LANGENDORFF (1)
LEAD OPTIMIZATION (1)
LEGO MINDSTORMS SYSTEMS VERIFICATION (1)
LEGO RCX BRICKS (1)
MATCHING (1)
MAXIMAL ELECTROSHOCK SEIZURES THRESHOLD (1)
MODEL CHECKING (1)
MULTIPROGRAMMING (1)
NICOTINIC ACETYLCHOLINE RECEPTORS (1)
NOVEL OBJECT RECOGNITION (1)
PATCH CLAMP (1)
POSITIVE ALLOSTERIC MODULATOR (1)
POTASSIUM CHANNEL (1)
PROGRAM VERIFICATION (1)
REAL TIME CONTROL PROGRAMS (1)
REAL TIME SYSTEM (1)
REAL TIME SYSTEMS (1)
REAL-TIME SYSTEMS (1)
SCHEDULING (1)
SCNA1 (1)
SLICE ELECTROPHYSIOLOGY (1)
STRUCTURAL ANALYSIS (1)
TEMPERATURE (1)
TIMED AUTOMATA MODEL (1)
TORSADES DE POINTES (1)
UPPAAL (1)
VERIFICATION TOOL (1)
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Elsevier (9)
Wiley (2)
DML (1)
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Search results for: Morten Laursen

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