• Pain · Dec 2006

    Tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium channels.

    • Gertrud Haeseler, Nilufar Foadi, Jörg Ahrens, Reinhard Dengler, Hartmut Hecker, and Martin Leuwer.
    • Department of Anesthesiology, Hannover Medical School, Germany. Haeseler.Gertrud@MH-Hannover.de
    • Pain. 2006 Dec 15; 126 (1-3): 234-44.

    AbstractLidocaine-like sodium channel blocking drugs provide pain relief either by interrupting impulse conduction in neurons when applied locally in high concentrations or, when given systemically, by suppressing high-frequency ectopic discharges due to preferential drug binding to inactivated channel states. Lidocaine-like actions of opioids have frequently been demonstrated clinically. However, drug binding to resting and inactivated channel conformations has been studied systematically only in the case of meperidine. The aim of this in vitro study was to investigate the effects of four currently used opioids on heterologously expressed neuronal (NaV(1.2)) voltage-gated sodium channels. Block of sodium currents was studied at hyperpolarized holding potentials and at depolarized potentials inducing either fast- or slow-inactivation. Sufentanil, fentanyl and tramadol but not morphine reversibly suppressed sodium inward currents at high concentrations (half-maximum blocking concentrations (IC50) 49+/-4, 141+/-6 and 103+/-8 microM) when depolarizations were started from hyperpolarized holding potentials. Short depolarizations inducing fast-inactivation and long prepulses inducing slow-inactivation significantly (*p < or = 0.001) increased the blocking potency for these opioids. 15% slow inactivated channels reduced the respective IC50 values to 5+/-3, 12+/-2 and 21+/-2 microM. These results show that: (1) Sufentanil, fentanyl and tramadol block voltage-gated sodium channels with half-maximum inhibitory concentrations similar to the IC50 reported for meperidine. (2) Slow inactivation--a physiological mechanism to suppress ectopic activity in response to slow shifts in membrane potential--increases binding affinity for sufentanil, fentanyl and tramadol. (3) Morphine has no such effects.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…