The atypic antipsychotic clozapine inhibits multiple cardiac ion channels.

Clozapine is an atypical neuroleptic used to manage treatment-resistant schizophrenia which is known to inhibit cardiac hERG/K11.1 potassium channels, a pharmacological property associated with increased risk of potentially fatal Torsades de Pointes (TdP) and sudden cardiac death (SCD). Yet, the long-standing clinical practice of clozapine does not show a consistent association with increased incidence of TdP, although SCD is considerably higher among schizophrenic patients than in the general population.

The grapefruit polyphenol naringenin inhibits multiple cardiac ion channels.

Drinking fresh grapefruit juice is associated with a significant prolongation of the QT segment on the electrocardiogram (ECG) in healthy volunteers. Among the prominent polyphenols contained in citrus fruits and primarily in grapefruit, the flavonoid naringenin is known to be a blocker of the human ether-a-go-go related gene (hERG) potassium channel. Here we hypothesized that naringenin could interfere with other major ion channels shaping the cardiac ventricular action potential (AP).

Cannabidiol inhibits multiple cardiac ion channels and shortens ventricular action potential duration in vitro.

Cannabidiol (CBD) is a non-psychoactive component of Cannabis which has recently received regulatory consideration for the treatment of intractable forms of epilepsy such as the Dravet and the Lennox-Gastaut syndromes. The mechanisms of the antiepileptic effects of CBD are unclear, but several pre-clinical studies suggest the involvement of ion channels. Therefore, we have evaluated the effects of CBD on seven major cardiac currents shaping the human ventricular action potential and on Purkinje fibers isolated from rabbit hearts to assess the in vitro cardiac safety profile of CBD.