The local anesthetic butamben inhibits total and L-type barium currents in PC12 cells.
BACKGROUND
Butamben or n-butyl-p-aminobenzoate is a long-acting experimental local anesthetic for the treatment of chronic pain when given as an epidural suspension. We have investigated whether Cav1.2/L-type calcium channels may be a target of this butamben action.


METHODS
The effect of butamben on these channels was studied in undifferentiated rat PC12-cells with the whole-cell patch-clamp technique in voltage-clamp. Ba(2+) ions were used as the charge carriers in the calcium channel currents, whereas K(+) currents were removed using K(+) free solutions.


RESULTS
Butamben 500 microM reversibly suppressed the total whole-cell barium current by 90% +/- 3% (n = 15), whereas 10 microM nifedipine suppressed this barium current by 75% +/- 7% (n = 6). Preexposure to butamben followed by washout decreased the inhibition by nifidepine to 47% +/- 5% (n = 10). These suppressive effects were not due to the measurement procedure and the drug vehicles in the solutions (<0.1% ethanol; n = 6).


CONCLUSIONS
Butamben inhibits the total barium current through expressed calcium channel types in PC12 cells, including Cav1.2/L-type channels. Because Cav1.2 channels may also occur in human nociceptive C fibers, this result allows the possibility that these L-type channels are involved in the analgesic action of butamben.
Rampaart
Laurentius J A
LJ
Department of Neurophysiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Beekwilder
Jeroen P
JP
van Kempen
Gertrudis Th H
GT
van den Berg
Rutgeris J
RJ
Ypey
Dirk L
DL
D000700:Analgesics / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000378:metabolism*; D001566:Benzocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D051381:Rats
D000700:Analgesics; D000779:Anesthetics, Local; C504728:Cacna1c protein, rat; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D001464:Barium; C004605:butamben; D009543:Nifedipine; D001566:Benzocaine