Effects of 4-Aminopyridine on Cloned hERG Channels Expressed in Mammalian Cells.

Archives of Drug Information
Muthukrishnan RenganathanA R Blight

Abstract

INTRODUCTION: Non-clinical evaluation of a medication's potential to induce cardiac toxicity is recommended by regulatory agencies. 4-Aminopyridine (fampridine) is a potassium channel blocker with the demonstrated ability to improve walking ability in patients with multiple sclerosis. We evaluated the in vitro effects of 4-aminopyridine on the human ether-à-go-go-related gene (hERG) channel current, since hERG current inhibition is associated with QT interval prolongation-a precursor to torsade de pointes (TdP). METHODS: 4-Aminopyridine was evaluated in concentrations ranging from 0.1 mM to 30 mM in human embryonic kidney 293 cells stably transfected with the hERG gene; terfenadine 60 nM was used as a positive control. RESULTS AND DISCUSSION: We observed concentration-dependent inhibition of hERG current with 4-aminopyridine doses between 0.3 and 30 mM. The concentration of 3.8 mM resulting in 50% inhibition (IC(50)) is approximately three orders of magnitude higher than expected therapeutic plasma concentrations, suggesting 4-aminopyridine has low potential for prolonging QT interval or inducing TdP.

References

Jun 1, 1996·Journal of Neurophysiology·M S GoldJ D Levine
Mar 25, 1999·Journal of Cardiovascular Electrophysiology·S Nattel
Jul 22, 1999·Annals of the New York Academy of Sciences·W A CoetzeeB Rudy
Apr 20, 2004·Journal of Cardiovascular Electrophysiology·Robert R FenichelUNKNOWN Independent Academic Task Force
Jan 8, 2005·European Heart Journal·M L De BruinH G M Leufkens
Nov 10, 2005·The Journal of Pharmacology and Experimental Therapeutics·Alexander N KatchmanSteven N Ebert
Feb 15, 2007·Expert Opinion on Therapeutic Targets·Harry J Witchel
Apr 19, 2007·Multiple Sclerosis : Clinical and Laboratory Research·A D GoodmanA R Blight
Aug 2, 2008·Neurology·A D GoodmanUNKNOWN Fampridine MS-F202 Study Group

❮ Previous
Next ❯

Citations

Jul 12, 2012·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·Andrew M KingAnthony F Pizon
Nov 20, 2012·Current Medical Research and Opinion·Scott WeirHerbert R Henney
Apr 14, 2012·Clinical Therapeutics·David R CornblathAndrew R Blight
Apr 30, 2010·Archives of Drug Information·George ThomasAndrew Blight
Mar 4, 2014·Therapeutic Advances in Neurological Disorders·Henrik Boye JensenEgon Stenager
Apr 2, 2016·Antonie van Leeuwenhoek·Khadidja AlilicheAli Chriki
Oct 16, 2020·Neurodegenerative Disease Management·Laura De GiglioElena Maria Pennisi

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection

Software Mentioned

Solver
pCLAMP
Excel

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.