Voltage-gated sodium channel blocker

Anget T, Madge DJ, Mulla M, Riddall D, Medicinal Chemistty of Neuronal Voltage-Gated Sodium Channel Blockers,Chem 44 115—137, 2001. 

Anger, T., Madge, D. J., Mulla, M., Riddal, D. Medicinal chemistry of neuronal voltage-gated sodium channel blockers, J. Med. Chem. 2001, 44, 115-137. 

Huang CJ, Harootunian A, Maher MP, Quan C, Raj CD, McCormack K, et al. Characterization of voltage-gated sodium-channel blockers by electrical stimulation and fluorescence detection of membrane potential. Nat Biotechnol 2006 24 439-46. 

Saxitoxin Voltage-gated sodium channel blocker... 

Saxitoxins are selective, reversible, voltage-gated sodium channel blockers (Huot et al., 1989 Tarnawa et al., 2007 Walker et al., 2013). Saxitoxins cross the blood-brain barrier, and sodium channel blockade in the CNS contributes to its paralytic effects (Borison and McCarthy, 1977). Saxitoxins are extremely potent, with mouse LD50 values of 263pg/kg (oral), lOpg/kg (intraperitoneal), and 3.4pg/kg (intravenous) (Wiberg and Stephenson, 1960). 

J. R., Nakamura, L., Monaghan, E. P., Ramu, K. Characterization of the anticonvulsant and pharmacokinetic properties of Co102862, a novel blocker of voltage-gated sodium channels, Epilepsia 1997, 28, suppl 8, 1038. 

Fig. 6.14 Structure of kalkitoxin, a potent voltage-gated sodium channel (VGSC) blocker.

Silperisone (32) is a sodium channel blocker acting centrally as a muscle relaxant. The compormd has been in preclinical animal studies [81, 82] and has been proposed recently to have potential as an antispastic drug in demyelinating diseases such as multiple sclerosis. In vivo, silperisone depressed ventral root reflexes and excitability of motoneurons. Whole-cell measurements in dorsal root ganglion cells revealed that silperisone depressed voltage gated sodium channel conductance at concentrations that inhibited spinal reflexes. 

Tarnawa, L, Bolcskei, H., Kocsis, P, 2007. Blockers of voltage-gated sodium channels for the treatment of central nervous system diseases. Recent Pat. CNS Drug Discov. 2 (1), 57—78. 

Hedrich R, Marten I (2011) TPCl-SV channels gain shape. Mol Plant 4 428 41 Huang CJ, Moczydlowski E (2001) Cytoplasmic polyamines as permeant blockers and modulators of the voltage-gated sodium channel. Biophys J 80 1262-1279 Hughes G, Khan YM, East M, Lee AG (1995) Effects of polycations on Ca binding to the Ca -ATPase. Biochem J 308 493—499... 

Figure 4. Whole-cell currents recorded from an axolotl vomeronasal receptor neuron in an epithelial slice. Currents were elicited by applying a series of voltage pulses, fiom -80 mV to +60 mV, in 10 mV increments. Vhoid = -80 mV. (A) Currents recorded in standard amphibian physiological saline, before any channel blockers were washed onto the slice. (B) Currents recorded 3 min after 10 pM tetrodotoxin (TTX) was washed onto the cell. TTX blocks voltage-gated sodium currents, revealing a second inward current. (C) Currents recorded 9 min after a solution containing both 10 pM TTX and 1 mM CoCk was washed onto the slice. Cobalt blocks calcium currents, demonstrating that the rapidly-inactivating inward current shown in panel B was carried by calcium.

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