Antinociceptive efficacy of lacosamide in a rat model for painful diabetic neuropathy

Beyreuther, B.; Callizot, Noëlle; Stöhr, Thomas

doi:10.1016/j.ejphar.2006.04.009

Cited by 99 publications

(55 citation statements)

References 23 publications

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“…The classic sodium channel-modulating anticonvulsants are relatively inactive in the 6-Hz psychomotor model of treatment-resistant seizures (Barton et al, 2001), whereas LCM has shown full efficacy in this test (Beyreuther et al, 2007). Moreover, LCM has been compared with LTG in the streptozotocin model for diabetic neuropathic pain (Beyreuther et al, 2006). Although LCM showed full efficacy against mechanical hyperalgesia and thermal allodynia, LTG was completely inactive.…”

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

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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.

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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

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399

345

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“…In animal models, levetiracetam has been shown to induce antihyperalgesic effects in the chronic constriction injury model 17 and streptozocin-induced diabetic rats. [17][18][19] It is possible that the pharmacological action of levetiracetam does not interfere with central pain mechanisms. This is in accordance with the experimental study finding no effect of levetiracetam on temporal pain summation.…”

Section: Discussionmentioning

confidence: 99%

“…[14][15][16] In animal models of peripheral neuropathic pain, levetiracetam has been shown to induce antinociceptive effects. [17][18][19] In experimental human pain models, levetiracetam increased pain tolerance thresholds but had no effect on temporal pain summation. 20 An open-label study and case reports suggest efficacy of levetiracetam in postherpetic neuralgia, 21 painful polyneuropathy, 22 neoplastic plexopathies 23 and central neuropathic pain and spasms in multiple sclerosis.…”

Section: Introductionmentioning

confidence: 99%

Levetiracetam in spinal cord injury pain: a randomized controlled trial

et al. 2009

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Study design: A randomized, double-blind, placebo-controlled, crossover, multicenter trial. A 1-week baseline period was followed by two treatment periods of 5 weeks duration with levetiracetam increased from 500 mg b.i.d. to a maximum of 1500 mg b.i.d. separated by a 1-week washout period. Objectives: The objective of the study was primarily to evaluate the efficacy of the anticonvulsant levetiracetam in patients with spinal cord injury (SCI) at-and below-level pain and secondarily to evaluate the effect on spasm severity. Setting: Outpatients at two spinal cord units and a pain center. Methods: Patients were allowed to continue their usual pain treatment at a constant dose. The primary outcome measure was the change in median daily pain score (on a 0-10 point numeric rating scale) from 1-week baseline period to the last week of each treatment period. Secondary outcome measures included pain relief of at-and below-level pain, allodynia, spasms and spasticity. Results: A total of 36 patients with SCI at-and or below-level pain were enrolled. Of these, 24 patients completed the trial. We found no effect of levetiracetam on the primary (P ¼ 0.46) or any of the secondary outcome measures. Only two patients continued levetiracetam treatment following the trial, and one patient was still in levetiracetam treatment at the 6-month follow-up. Levetiracetam was generally well tolerated with no serious adverse events. Conclusions: Levetiracetam does not relieve neuropathic pain or spasm severity following spinal cord injury.

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“…En modelos experimentales en animales, la actividad analgésica de lacosamida se ha examinado extensamente en una amplia variedad de estados de dolor neuropático inducidos de forma artificial. Cuando se administra a ratas con neuropatía diabética inducida por la administración de estreptozotocina, las hiperalgesias térmicas y mecáni-cas inducidas son reducidas por la administración de la lacosamida (20). De forma similar, la administración de lacosamida a ratas que han sufrido una lesión isquémica del nervio infraorbitario o de la médula espinal ocasiona una reducción de la hipersensibilidad mecánica (21).…”

Section: Lacosamida Y Dolor Neuropáticounclassified

Lacosamida en el tratamiento del dolor neuropático

Montero¹,

Curado²

2016

Rev. Soc. Esp. Dolor.

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Rev Soc Esp Dolor 2016; 23(6): 316-325Recibido: 30-11-15. Aceptado: 20-02-16. Dolor 2016;23(6):316-325. Alcántara Montero A y González Curado A. Lacosamida en el tratamiento del dolor neuropático. Rev Soc Esp ABSTRACTMost of the clinical practice guidelines consulted agree that tricyclics, dual (venlafaxine/duloxetine) antidepressants, gabapentin/pregabalin antiepileptics, lidocaine 5 % patches and capsaicin 8 % patches are the first-line drugs in the treatment of peripheral neuropathic pain, being tramadol and some strong opioids (morphine, oxycodone and tapentadol) second-line drugs treatment. Moreover, the prevalence of neuropathic pain refractory to treatment is about 1,5 % of the population, so that an estimated 50 % of patients not responding to prescribed treatment. There are other antiepileptics who not have neuropathic pain indication by regulatory agencies, such as lamotrigine, topiramate or oxcarbazepine, but are used in routine clinical practice off-label.Although not approved the use of lacosamide in the treatment of neuropathic pain, some authors believe that could be a good option for patients who do not respond to standard treatments.The following article summarizes the main pharmacological characteristics of lacosamide as well as the literature available in neuropathic pain.Key words: Lacosamide, neuropathic pain. RESUMENLa mayor parte de las guías de práctica clínica consultadas coinciden en señalar que los antidepresivos tricíclicos, duales (venlafaxina/duloxetina), los antiepilépticos gabapentina/pregabalina, apósitos de lidocaína 5 % y parches de capsaicina 8 % constituyen los fármacos de primera línea en el tratamiento del dolor neuropático periférico, siendo el tramadol y algunos opioides potentes (morfina, oxicodona y tapentadol) fármacos de segunda línea de tratamiento. Por otra parte, la prevalencia de dolor neuropático refractario al tratamiento se acerca al 1,5 % de la población, de forma que se calcula que un 50 % de los pacientes no responde al tratamiento prescrito. Existen otros antiepilépticos que no tienen indicación en dolor neuropático por las agencias reguladoras, como la lamotrigina, topiramato u oxcarbazepina, pero se utilizan en la práctica clínica habitual fuera de indicación.Aunque no está aprobado el uso de lacosamida en el tratamiento del dolor neuropático, algunos autores consideran que podría ser una buena opción para aquellos pacientes que no responden a los tratamientos habituales.En el siguiente artículo se resumen las principales características farmacológicas de lacosamida, así como la bibliografía disponible en dolor neuropático.Palabras clave: Lacosamida, dolor neuropático. INTRODUCCIÓNSe define el dolor neuropático (DN) como el dolor que aparece como consecuencia directa de una lesión o enfermedad del sistema somatosensorial (1). El DN crónico no tiene función biológica alguna, e impone con frecuencia alteraciones físicas, emocionales, sociales y económicas, las cuales dificultan profundamente la vida de los pacientes que lo sufren. Es un problema clínico imp...

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Antinociceptive efficacy of lacosamide in a rat model for painful diabetic neuropathy

Cited by 99 publications

References 23 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

Levetiracetam in spinal cord injury pain: a randomized controlled trial

Lacosamida en el tratamiento del dolor neuropático

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