Antiepileptic Drug Tiagabine Does Not Directly Target Key Cardiac Ion Channels Kv11.1, Nav1.5 and Cav1.2.
Action Potentials
Animals
Anticonvulsants
/ adverse effects
Calcium Channels, L-Type
/ chemistry
Computer Simulation
ERG1 Potassium Channel
/ antagonists & inhibitors
Epilepsy
/ complications
Heart
/ drug effects
Humans
Male
Molecular Docking Simulation
/ methods
NAV1.5 Voltage-Gated Sodium Channel
/ chemistry
Rats
Rats, Wistar
Tiagabine
/ adverse effects
ECG study
cardiac voltage-gated ion channels
molecular modeling
tiagabine
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
09 Jun 2021
09 Jun 2021
Historique:
received:
22
04
2021
revised:
01
06
2021
accepted:
08
06
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
30
7
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34207748
pii: molecules26123522
doi: 10.3390/molecules26123522
pmc: PMC8226520
pii:
doi:
Substances chimiques
Anticonvulsants
0
Calcium Channels, L-Type
0
ERG1 Potassium Channel
0
L-type calcium channel alpha(1C)
0
NAV1.5 Voltage-Gated Sodium Channel
0
Tiagabine
Z80I64HMNP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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