title: Inhibition of L-type calcium current by tramadol and enantiomers in cardiac myocytes from rats.
abstract: 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 (ICa-L).
  
  
  METHODS
  The experiments were carried out in isolated Wistar rat ventricular myocytes by using the whole cell patch clamp technique.
  
  
  RESULTS
  Tramadol (200 µM) reduced the peak amplitude of ICa-L at potentials from 0 to +50 mV. At 0 mV, I(Ca-L) was reduced by 33.7 ± 7.2%. (+)- and (-)-tramadol (200 µM) 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 (p > 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 I(Ca-L) to the right and slowed down the recovery of I(Ca-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 µ-opioid receptor DAMGO had no effect on the I(Ca-L).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Medei
authors.forename: Juliana M
authors.initials: JM
authors.lastname: Raimundo
authors.forename: José Hamilton M
authors.initials: JH
authors.lastname: Nascimento
authors.forename: Margarete M
authors.initials: MM
authors.lastname: Trachez
authors.forename: Roberto T
authors.initials: RT
authors.lastname: Sudo
authors.forename: Gisele
authors.initials: G
authors.lastname: Zapata-Sudo
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D003864:Depression, Chemical; D008297:Male; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D014147:Tramadol / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D020746:Calcium Channels, L-Type; D014147:Tramadol