Antiepileptic Drug Tiagabine Does Not Directly Target Key Cardiac Ion Channels Kv11.1, Nav1.5 and Cav1.2.
Magdalena KowalskaŁukasz FijałkowskiMonika KubackaKinga SałatGrzegorz GrześkJacek NowaczykAlicja NowaczykPublished in: Molecules (Basel, Switzerland) (2021)
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.
Keyphrases
- molecular docking
- left ventricular
- chronic pain
- adverse drug
- drug induced
- endothelial cells
- heart failure
- catheter ablation
- emergency department
- oxidative stress
- atrial fibrillation
- physical activity
- magnetic resonance
- high throughput
- risk factors
- sleep quality
- risk assessment
- combination therapy
- brain injury
- blood brain barrier
- smoking cessation
- cerebral ischemia
- dual energy