Antiepileptic Drug Tiagabine Does Not Directly Target Key Cardiac Ion Channels Kv11.1, Nav1.5 and Cav1.2
Magdalena Kowalska,
Łukasz Fijałkowski,
Monika Kubacka,
Kinga Sałat,
Grzegorz Grześk,
Jacek Nowaczyk,
Alicja Nowaczyk
Affiliations
Magdalena Kowalska
Department of Organic Chemistry, Faculty of Pharmacy, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
Łukasz Fijałkowski
Department of Organic Chemistry, Faculty of Pharmacy, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
Monika Kubacka
Department of Pharmacodynamics, Chair of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland
Kinga Sałat
Department of Pharmacodynamics, Chair of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland
Grzegorz Grześk
Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 75 Ujejskiego St., 85-168 Bydgoszcz, Poland
Jacek Nowaczyk
Physical Chemistry and Chemistry of Polymers, Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarina St., 87-100 Toruń, Poland
Alicja Nowaczyk
Department of Organic Chemistry, Faculty of Pharmacy, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
Tiagabine is an antiepileptic drug used for the treatment of partial seizures in humans. Recently, this drug has been found useful in several non-epileptic conditions, including anxiety, chronic pain and sleep disorders. Since tachycardia—an impairment of cardiac rhythm due to cardiac ion channel dysfunction—is one of the most commonly reported non-neurological adverse effects of this drug, in the present paper we have undertaken pharmacological and numerical studies to assess a potential cardiovascular risk associated with the use of tiagabine. A chemical interaction of tiagabine with a model of human voltage-gated ion channels (VGICs) is described using the molecular docking method. The obtained in silico results imply that the adverse effects reported so far in the clinical cardiological of tiagabine could not be directly attributed to its interactions with VGICs. This is also confirmed by the results from the isolated organ studies (i.e., calcium entry blocking properties test) and in vivo (electrocardiogram study) assays of the present research. It was found that tachycardia and other tiagabine-induced cardiac complications are not due to a direct effect of this drug on ventricular depolarization and repolarization.
