Analysis of the electrophysiologic effects of short-term oxybutynin on guinea pig and rabbit ventricular cells

The objective of this study was to investigate the cardioactive properties of oxybutynin, a drug that is widely prescribed for management of voiding dysfunction. Membrane currents were recorded from whole-cell- configured guinea pig ventricular myocytes, and action potentials were recorded from guinea pig and rabbit papillary muscles. L-type Ca²⁺ current (I(Ca,L)), inward-rectifier K⁺ current (I(K1)), and delayed-rectifier K⁺ current (I(K)) were unaffected by ≤1 μM oxybutynin, and inhibited by higher concentrations. The concentrations that reduced the currents to one-half of predrug control amplitude (K_0.5) were as follows: I(Ca,L), 16.1 μM, I(K1), 18.2 μM, rapidly activating I(K) (I(Kr)), 11.4 μM, and slowly activating I(K) (I(Ks)), 28.7 μM. Action-potential durations at 20 and 90% repolarization (APD₂₀, APD₉₀) were unaffected by oxybutynin ≤3 μM in guinea pig papillary muscles driven at 1 Hz; higher concentrations selectively shortened the APD₂₀ by as much as 25% (100) μM), and caused moderate reductions in maximal upstroke velocity. Changes in the action potentials of rabbit papillary muscles were even smaller than in the guinea pig muscles. Because the peak therapeutic plasma concentration of oxybutynin is in the 0.01-0.1 μM range, the results suggest that the drug is highly unlikely to have adverse effects on cardiac electrical activity.