Carbamazepine interacts with a slow inactivation state of NaV1.8-like sodium channels

Cardenas, Carla G.; Armendi, Alberto J. de; Scroggs, Reese S.

doi:10.1016/j.neulet.2006.08.070

Cited by 29 publications

(21 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently published studies suggest that certain opiate analgesics (Haeseler et al, 2006), carbamazepine (Cardenas et al, 2006), and a preclinical congener of DPH (Lenkowski et al, 2007) to some extent promote slow inactivation of VGSCs in dorsal root ganglion cells or central nervous system neurons. However, upon examination of the voltage-clamp experiments performed using these ligands, it is apparent that they all concurrently interact with fast inactivation (in contrast to LCM).…”

Section: Discussionmentioning

confidence: 99%

The Investigational Anticonvulsant Lacosamide Selectively Enhances Slow Inactivation of Voltage-Gated Sodium Channels

Errington

Stöhr²,

Heers³

et al. 2007

Mol Pharmacol

395

344

View full text Add to dashboard Cite

We hypothesized that lacosamide modulates voltage-gated sodium channels (VGSCs) at clinical concentrations (32-100 M). Lacosamide reduced spiking evoked in cultured rat cortical neurons by 30-s depolarizing ramps but not by 1-s ramps. Carbamazepine and phenytoin reduced spike-firing induced by both ramps. Lacosamide inhibited sustained repetitive firing during a 10-s burst but not within the first second. Tetrodotoxin-sensitive VGSC currents in N1E-115 cells were reduced by 100 M lacosamide, carbamazepine, lamotrigine, and phenytoin from V h of Ϫ60 mV. Hyperpolarization (500 ms) to Ϫ100 mV removed the block by carbamazepine, lamotrigine, and phenytoin but not by lacosamide. The voltage-dependence of activation was not changed by lacosamide. The inactive Sstereoisomer did not inhibit VGSCs. Steady-state fast inactivation curves were shifted in the hyperpolarizing direction by carbamazepine, lamotrigine, and phenytoin but not at all by lacosamide. Lacosamide did not retard recovery from fast inactivation in contrast to carbamazepine. Carbamazepine, lamotrigine, and phenytoin but not lacosamide all produced frequency-dependent facilitation of block of a 3-s, 10-Hz pulse train. Lacosamide shifted the slow inactivation voltage curve in the hyperpolarizing direction and significantly promoted the entry of channels into the slow inactivated state (carbamazepine weakly impaired entry into the slow inactivated state) without altering the rate of recovery. Lacosamide is the only analgesic/anticonvulsant drug that reduces VGSC availability by selective enhancement of slow inactivation but without apparent interaction with fast inactivation gating. The implications of this unique profile are being explored in phase III clinical trials for epilepsy and neuropathic pain.

show abstract

Section: Discussionmentioning

confidence: 99%

The Investigational Anticonvulsant Lacosamide Selectively Enhances Slow Inactivation of Voltage-Gated Sodium Channels

Errington

Stöhr²,

Heers³

et al. 2007

Mol Pharmacol

395

344

View full text Add to dashboard Cite

show abstract

“…More recently, Song et al (2009) showed that B1 vitamin treatment reduced neuronal hyperexcitability and lessen alterations of Na + currents in injured dorsal root ganglia, and proposed that such mechanisms might contribute to its thermal antihyperalgesic effect. Considering that blockade of voltagedependent Na + channels in hyperexcitable neurons of the dorsal root or trigeminal ganglia has also been implicated in the analgesic effect of anticonvulsant drugs in neuropathic pain (Cardenas et al, 2006;Caviedes and Herranz, 2002;Priest, 2009), the antihyperalgesic synergism between carbamazepine and B vitamins may be the result of their combined action on this common target. However, the differential effects of the vitamins depending on the type of stimulus used Fig.…”

Section: Discussionmentioning

confidence: 99%

B vitamins relieve neuropathic pain behaviors induced by infraorbital nerve constriction in rats

Kopruszinski

Reis

2012

Life Sciences

View full text Add to dashboard Cite

show abstract

“…This result is not surprising for lacosamide due to its ineffectiveness on fast inactivation of Na v 1.7 and Na v 1.3 channels, but it is somewhat surprising for lidocaine and carbamazepine. However, previous studies have indicated that lidocaine does not alter fast inactivation of Na v 1.8 channels in the same manner that it does Na v 1.7 channels (Chevrier et al, 2004) and that carbamazepine might even preferentially target slowinactivated Na v 1.8 channels (Cardenas et al, 2006). This raises the possibility that access to the drug-binding site in fast-inactivated state of Na v 1.8-type channels might be substantially different from the site in Na v 1.7 and Na v 1.3 channels.…”

Section: Inhibition Of Sensory Sodium Channels By Lacosamide 95mentioning

confidence: 91%

Differential Block of Sensory Neuronal Voltage-Gated Sodium Channels by Lacosamide [(2R)-2-(Acetylamino)-N-benzyl-3-methoxypropanamide], Lidocaine, and Carbamazepine

Sheets

Heers²,

Stoehr³

et al. 2008

J Pharmacol Exp Ther

175

187

View full text Add to dashboard Cite

Voltage-gated sodium channels play a critical role in excitability of nociceptors (pain-sensing neurons). Several different sodium channels are thought to be potential targets for pain therapeutics, including Na v 1.7, which is highly expressed in nociceptors and plays crucial roles in human pain and hereditary painful neuropathies, Na v 1.3, which is up-regulated in sensory neurons following chronic inflammation and nerve injury, and Na v 1.8, which has been implicated in inflammatory and neuropathic pain mechanisms. We compared the effects of lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide], a new pain therapeutic, with those of lidocaine and carbamazepine on recombinant Na v 1.7 and Na v 1.3 currents and neuronal tetrodotoxin-resistant (Na v 1.8-type) sodium currents using whole-cell patch-clamp electrophysiology. Lacosamide is able to substantially reduce all three current types. However, in contrast to lidocaine and carbamazepine, 1 mM lacosamide did not alter steadystate fast inactivation. Inhibition by lacosamide exhibited substantially slower kinetics, consistent with the proposal that lacosamide interacts with slow-inactivated sodium channels. The estimated IC 50 values for inhibition by lacosamide of Na v 1.7-, Na v 1.3-, and Na v 1.8-type channels following prolonged inactivation were 182, 415, and 16 M, respectively. Na v 1.7-, Na v 1.3-, and Na v 1.8-type channels in the resting state were 221-, 123-, and 257-fold less sensitive, respectively, to lacosamide than inactivated channels. Interestingly, the ratios of resting to inactivated IC 50 s for carbamazepine and lidocaine were much smaller (ranging from 3 to 16). This suggests that lacosamide should be more effective than carbamazepine and lidocaine at selectively blocking the electrical activity of neurons that are chronically depolarized compared with those at more normal resting potentials.

show abstract

Carbamazepine interacts with a slow inactivation state of NaV1.8-like sodium channels

Cited by 29 publications

References 24 publications

The Investigational Anticonvulsant Lacosamide Selectively Enhances Slow Inactivation of Voltage-Gated Sodium Channels

The Investigational Anticonvulsant Lacosamide Selectively Enhances Slow Inactivation of Voltage-Gated Sodium Channels

B vitamins relieve neuropathic pain behaviors induced by infraorbital nerve constriction in rats

Differential Block of Sensory Neuronal Voltage-Gated Sodium Channels by Lacosamide [(2R)-2-(Acetylamino)-N-benzyl-3-methoxypropanamide], Lidocaine, and Carbamazepine

Contact Info

Product

Resources

About