Figure 1 The effects of terfenadine on action potential duration.


Figure1 shows action potential records taken from a single left ventricular myocyte under our standard experimental conditions used for the action potential measurements in the absence (black) and presence (red) of terfenadine (1 and 10 鮼br>
The effect of terfenadine (0.01 튠 30 mM) on action potential configuration are more complex than other compounds.  
At low concentrations terfenadine caused significant prolongation of APD90.  APD90 was prolonged by 9.5 䮲% by 100 nM terfenadine and by 10.6 튠 3.2% by 1 ഥrfenadine (see Fig 1A).  
However, at higher concentrations terfenadine caused a decreased APD90 at 1 Hz: there was a 36.8 ⮰ % decrease at 10 ࡮d a 71.2 ᰮ5 % decrease at 30 ഥrfenadine (see Fig 1B).

The action potential shortening effects of terfenadine at the higher concentrations were associated with depression of the plateau and triangulation of action potential configuration (see Fig 1B), though this was not obvious from measurements of APD50, which showed broadly similar concentration-dependent changes as those seen in APD90. At concentrations of 1 ࡮d above, terfenadine caused a significant, concentration-dependent decrease in MRD (P<0.05).  At 1  നere was a 9.9 㮱 % decrease in MRD, at 10  നere was a 53.9 ⮳ % decrease, and at 30  നere was a 69.3 ⮱ % decrease.


Figure 2   Mean data for the effect of terfenadine on APD50 and APD90.


Figure 2 shows that the effects of terfenadine are more complex than the effects of other compounds described on this site.  A significant prolongation of APD90 was detected at 100 nM and 1 mM, but these effects did not increase in a concentration-dependent manner, but rather reversed, such that at higher concentrations of terfenadine, 10 ࡮d 30 젡 significant shortening of APD90 was observed (see Fig 1B and Fig 2).  It therefore appears that the actions of terfenadine may differ from those of the comparator compounds, dofetilide and sotalol.

Action potential configuration is determined by the complex interaction of a variety of ionic currents.  Terfenadine has been shown to inhibit IKr (Woosley, et. al, 1993), which is expected to cause action potential prolongation, but also to inhibit cardiac calcium and sodium channels (Ming and Nordin, 1995), effects which are expected to shorten action potential duration (Coraboeuf, 1979 and Zhang et al., 1997). 

Therefore, it seems likely that the biphasic effect on action potential duration reflects effects on all of these cardiac ion channels.  Further evidence for this is provided by the observation that MRD was reduced by terfenadine at the higher concentrations (53.9 ⮳ % decrease at 10 鬠consistent with a reduction of sodium current which could contribute to the shortening of APD.




Woosley, R.L., Chen, Y.,Freiman, J.P. and Gillis, R.A. (1993). Mechanism of the cardiotoxic actions of terfendine. JAMA, 269:

Zhang S., Sawanobori, T., Hirano, Y. and Hiraoka, M. (1997). Multiple modulations of action potential duration by calcium channel blocking agents in guinea-pig ventricular myocytes. J Cardiovasc Pharmacol. 30:489-496.

Coraboeuf E, Deroubaix E, Coulombe A (1979). Effect of tetrodotoxin on action potentials of the conducting system in the dog heart. Am J Physiol. 236(4):H561-7.

Ming Z, Nordin C. (1995). Terfenadine blocks time-dependent Ca2+, Na+, and K+ channels in guinea pig ventricular myocytes. J Cardiovasc Pharmacol. 26(5):761-9.

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