Inhibition of L-type calcium current by tramadol and enantiomers in cardiac myocytes from rats.

Background: Tramadol is a centrally acting analgesic, whose mechanism of action involves opioid-receptor activation. Previously, we have shown that tramadol and its enantiomers had a negative inotropic effect on the papillary muscle in which the (+)-enantiomer is more potent than (-)- and (+/-)-tramadol. Objective: In this study, we investigated the effects of tramadol and its enantiomers on L-type calcium current Methods: The experiments were carried out in isolated Wistar rat ventricular myocytes by using the whole cell patch clamp technique. Results: Tramadol (200 mu M) reduced the peak amplitude of ICa-L at potentials from 0 to +50 mV. At 0 mV, ICa-L was reduced by 33.7 +/- 7.2%. (+)- and (-)-tramadol (200 mu M) produced a similar inhibition of ICa-L, in which the peak amplitude was reduced by 64.4 +/- 2.8% and 68.9 +/- 5.8%, respectively at 0 mV Ip > 0.05). Tramadol, (+)- and (-)-tramadol shifted the steady-state inactivation of ICa-L to more negative membrane potentials. Also, tramadol and (+)-tramadol markedly shifted the time-dependent recovery curve of ICa-L to the right and slowed down the recovery of ICa-L from inactivation. The time constant was increased from 175.6 +/- 18.6 to 305.0 +/- 32.9 ms (p < 0.01) for tramadol and from 248.1 +/- 28.1 ms to 359.0 +/- 23.8 ms (p < 0.05) for (+)-tramadol. The agonist of mu-opioid receptor DAMGO had no effect on the ICa-L. Conclusion: The inhibition of ICa-L induced by tramadol and its enantiomers was unrelated to the activation of opioid receptors and could explain, at least in part, their negative cardiac inotropic effect. (Arq Bras Cardiol 2011; 97(4):324-330)