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 < or = 1 microM oxybutynin, and inhibited by higher concentrations. The concentrations that reduced the currents to one-half of predrug control amplitude (K0.5) were as follows: 1(Ca),L, 16.1 microM, I(K1), 18.2 microM, rapidly activating I(K)(I(Kr)), 11.4 microM, and slowly activating I(K)(I(Ks)), 28.7 microM. Action-potential durations at 20 and 90% repolarization (APD20, APD90) were unaffected by oxybutynin < or =3 microM in guinea pig papillary muscles driven at 1 Hz; higher concentrations selectively shortened the APD20 by as much as 25% (100 microM), 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 microM range, the results suggest that the drug is highly unlikely to have adverse effects on cardiac electrical activity.
Jones
S E
SE
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
Kasamaki
Y
Y
Shuba
L M
LM
Ogura
T
T
McCullough
J R
JR
McDonald
T F
TF
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors
D008333:Mandelic Acids; D010276:Parasympatholytics; C005419:oxybutynin; D011188:Potassium; D002118:Calcium