On the relationship between block of the cardiac Na⁺ channel and drug-induced prolongation of the QRS complex.

ABSTRACT:

Background and purpose

Inhibition of the human cardiac Na(+) channel (hNa(v) 1.5) can prolong the QRS complex and has been associated with increased mortality in patients with underlying cardiovascular disease. The safety implications of blocking hNa(v) 1.5 channels suggest the need to test for this activity early in drug discovery in order to design out any potential liability. However, interpretation of hNa(v) 1.5 blocking potency requires knowledge of how hNa(v) 1.5 block translates into prolongation of the QRS complex.

Experimental approach

We tested Class I anti-arrhythmics, other known QRS prolonging drugs and drugs not reported to prolong the QRS complex. Their block of hNa(v) 1.5 channels (as IC(50) values) was measured in an automated electrophysiology-based assay.

SUBMITTER: Harmer AR 

PROVIDER: S-EPMC3174407 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature