Overview
- Bajaj, P. et al. (2003) Eur. J. Pain 7, 407.
- Meilinger, M. et al. (2003) Annals of the Rheumatic Diseases 62, 295.
- Kocsis, P. et al. (2005) J. Pharmacol. Exp. Ther. 315, 1237.
- Hofer, D. et al. (2006) Eur. J. Pharmacol. 538, 5.
Alomone Labs Tolperisone hydrochloride inhibits NaV1.2 channels expressed in Xenopus oocytes.A. Time course of current reversible inhibition by 0.2 mM and 1 mM Tolperisone hydrochloride (#T-115). Currents were elicited by a voltage step to 20 mV (100 ms) every 10 seconds from a holding potential of -80 mV. B. Example traces of current response to voltage step application before and during 1 mM Tolperisone hydrochloride application.
Voltage-gated Na+ channels (VGSC, NaV) are critically important for electrogenesis and nerve impulse conduction. Certain Na+ channel isoforms are predominantly expressed in peripheral sensory neurons associated with pain sensation, and the expression and functional properties of NaV in peripheral sensory neurons can be dynamically regulated following axonal injury or peripheral inflammation1.
Tolperisone is a centrally acting muscle relaxant (muscle relaxant acting on spasticity by interaction with upper motor neurons), which is also used for the treatment of chronic pain2-3. It is mainly used for treating muscle spasticities of neurological origin and painful muscle spasms due to rheumatologic conditions. Besides being an effective antispastic agent4-5, tolperisone also has analgesic activity in rodents6 and in humans7. It possesses relatively few side effects in humans5.
Tolperisone is an ion channel blocker that acts, at micromolar concentrations, as an acute blocker of seven different isoforms of NaV expressed in Xenopus oocytes. The drug concentrations needed to exert 50% block differ between the different isoforms are 116, 802, 96, 131, 326, 394 and 49 µM for NaV1.2, NaV1.3, NaV1.4, NaV1.5, NaV1.6, NaV1.7 and NaV1.8 channel, respectively8,9. NaV1.8, which is the most prominently affected channel, is known to be upregulated in an animal model of neuropathic pain10. The inhibitory effect is reversible and develops rapidly, with an IC50 value of 198 µM in dorsal root ganglion (DRG) cells11.
