Future Local Anesthetics – Neurotoxins?
Keywords:
Local anaesthetics, Neurotoxins.Abstract
The currently available local anaesthetics are non-specific blockers of the voltage gated sodium channels. Neurotoxins, derived from various sources are very potent and specific sodium channel blockers. Their site is also quite different from local anaesthetics. Their major toxic manifestation is muscle paralysis, which is easier to manage as compared to the serious cardiac and neurological side effects of local anaesthetics. These properties make neurotoxins almost an ideal local anaesthetic. A brief mention of the currently available neurotoxins and early studies with them are summarized.
References
Goldin AL, Barchi RL, Caldwell JH, Hofmann F, Howe JR, Hunter JC, et al. Nomenclature of voltage-gated sodium channels. Neuron 2000; 28: 365-8. http://dx.doi.org/10.1016/S0896-6273(00)00116-1
Mechanisms of (local) anaesthetics on voltagegated sodium and other ion channels. Scholz A. Br J Anaesth. 2002; 89(1): 52-61. http://dx.doi.org/10.1093/bja/aef163
Mar Drugs. Mar 2008; 6(2): 349–371. Neurotoxins from Marine Dinoflagellates: A Brief Review Da-Zhi Wang).
Stevens M, Peigneur S, Tytgat J. Neurotoxins and Their Binding Areas on Voltage-Gated Sodium Channels. Front Pharmacol. 2011; 2: 71. http://dx.doi.org/10.3389/fphar.2011.00071
Zhang MM, Gruszczynski P, Walewska A, Bulaj G, Olivera BM, Yoshikami D. Cooccupancy of the outer vestibule of voltage-gated sodium channels by -conotoxin KIIIA and saxitoxin or tetrodotoxin. J Neurophysiol. 2010; 104: 88-97. http://dx.doi.org/10.1152/jn.00145.2010
Butterworth JF. Will conventional local anesthetics soon be replaced by neurotoxins? (Editorial). Reg Anesth Pain Med. 2011; 36(2): 101-2. http://dx.doi.org/10.1097/AAP.0b013e31820db23e
Baer M, Best PM, Reuter H. Voltage dependant action of tetrodotoxin in mammalian cardiac muscle. Nature 1976; 263: 344-5. http://dx.doi.org/10.1038/263344a0
Strichartz G. Structural determinants of the affinity of saxitoxin for neuronal sodium channels. Electrophysiological studies on frog peripheral nerve. J Gen Physiol. 1984; 84: 281-305. http://dx.doi.org/10.1085/jgp.84.2.281
Kohane DS, Lu NT, Gokgol-Kline AC, Shubina M, Kuang Y, Hall S, et al. The local anesthetic properties and toxicity of saxitonin homologues for rat sciatic nerve block in vivo. Reg Anesth Pain Med. 2000; 25: 52-9. http://dx.doi.org/10.1097/00115550-200001000-00010
Suehiro M. Historical review on chemical and medical studies of globefish toxin before World War II. Jpn Soc Hist Pharm. 1994; 29: 428-434.
Bane V, Lehane M, Dikshit M, O’Riordan A, Furey A. Tetrodotoxin: Chemistry, Toxicity, Source, Distribution and Detection Toxins (Basel). 2014; 6(2): 693-755. http://dx.doi.org/10.3390/toxins6020693
Chau R, Kalaitzis JA, Neilan BA. On the origins and biosynthesis of tetrodotoxin. Aquat Toxicol. 2011; 104: 61-72. http://dx.doi.org/10.1016/j.aquatox.2011.04.001
Moran O, Picollo A, Conti F. Tonic and phasic guanidinium toxin-block of skeletal muscle Na channels expressed in Mammalian cells. Biophys J. 2003; 84: 2999-3006. http://dx.doi.org/10.1016/S0006-3495(03)70026-5
Wang GK, Srichartz GR. State dependent inhibition of sodium channels by local anesthetics: A 40 year evolution. Biochem (Mosc) Suppl Ser A Membr Cell Biol. 2012; 6(2): 120-127.
Kohane DS, Yieh J, Lu NT, Langer R, Strichartz GR, Berde CB. A re-examination of tetrodotoxin for prolonged duration local anesthesia. Anesthesiology 1998; 89: 119-31. http://dx.doi.org/10.1097/00000542-199807000-00019
Saoudi M, Abdelmouleh A, El Feki A. Tetrodotoxin: A potent marine toxin. Toxin Rev. 2010; 29: 60-70. http://dx.doi.org/10.3109/15569543.2010.487631
Hagen NA, du Souich P, Lapointe B, Ong-Lam M, Dubuc B, Walde D, et al. Canadian Tetrodotoxin Study Group Tetrodotoxin for moderate to severe cancer pain: a randomized, double blind, parallel design multicenter study. J Pain Symptom Manage. 2008; 35(4): 420-9. http://dx.doi.org/10.1016/j.jpainsymman.2007.05.011
Hagen NA, Fisher KM, Lapointe B, du Souich P, Chary S, Moulin D, et al. Canadian Tetrodotoxin Study Group An open-label, multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancerrelated pain. J Pain Symptom Manage. 2007; 34(2): 171-82. http://dx.doi.org/10.1016/j.jpainsymman.2006.11.008
Wiese M, D’Agostino PM, Mihali TK, Moffitt MC, Neilan BA. Neurotoxic Alkaloids: Saxitoxin and Its Analogs Mar. Drugs 2010; 8: 2185-2211.
Epstein-Barash H, Shichor I, Kwon AH, Hall S, Lawlor MW, Langer R, et al. Prolonged duration local anesthesia with minimal toxicity. Proc Natl Acad Sci USA 2009; 106: 7125- 7130. http://dx.doi.org/10.1073/pnas.0900598106
Chorny M, Levy RJ. Site-specific analgesia with sustained release liposomes. Proc Natl Acad Sci USA 2009; 106: 6891- 6892. http://dx.doi.org/10.1073/pnas.0903079106
Garrido R, Lagos N, Lagos M, Rodríguez-Navarro AJ, Garcia C, Truan D, et al. Treatment of chronic anal fissure by gonyautoxin. Colorectal Dis. 2007; 9: 619-624. http://dx.doi.org/10.1111/j.1463-1318.2006.01183.x
Kohane DS, Lu NT, Gokgol-Kline AC, Shubina M, Kuang Y, Hall S, et al. The local anesthetic properties and toxicity of saxitonin homologues for rat sciatic nerve block in vivo. Reg Anesth Pain Med. 2000; 25: 52-9. http://dx.doi.org/10.1097/00115550-200001000-00010
Strichartz G, Rando T, Hall S, Gitschier J, Hall L, Magnani B, et al. On the mechanism by which saxitoxin binds to and blocks sodium channels. Ann NY Acad Sci 1986; 479: 96- 112. http://dx.doi.org/10.1111/j.1749-6632.1986.tb15564.x
Alberto J, Rodriguez-Navarro AJ, Lagos N, Lagos M, Braghetto I, Csendes A. Neo saxitoxin as a local anesthetic. Anesthesiology 2007; 106: 339-45. http://dx.doi.org/10.1097/00000542-200702000-00023
Rodríguez-Navarro AJ, Berde CB, Wiedmaier G, Mercado A, Garcia C, Iglesias V, et al. Comparison of neosaxitoxin versus bupivacaine via port infiltration for postoperative analgesia following laparoscopic cholecystectomy. A randomized double -blind controlled trial. Reg Anesth Pain Med. 2011; 36(2): 103-9. http://dx.doi.org/10.1097/AAP.0b013e3182030662
Scanio MJ, Shi L, Drizin I, Gregg RJ, Atkinson RN, Thomas JB, et al. Discovery and biological evaluation of potent, selective, orally bioavailable, pyrazine-based blockers of the Na(v)1.8 sodium channel with efficacy in a model of neuropathic pain. Bioorg Med Chem. 2010; 18(22): 7816-25. http://dx.doi.org/10.1016/j.bmc.2010.09.057
Schmalhofer WA, Calhoun J, Burrows R, Bailey T, Kohler MG, Weinglass AB, et al. ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors. Pharmacology 2008; 74: 1476-84. http://dx.doi.org/10.1124/mol.108.047670
Halai R, Craik DJ. Conotoxins: Natural product drug leads. Nat Prod Rep. 2009; 26: 526-536. http://dx.doi.org/10.1039/b819311h
Klotz, U. Ziconotide—a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain—a short review. Int J Clin Pharmacol Ther. 2006; 44:478-483. http://dx.doi.org/10.5414/CPP44478
McGivern JG. Ziconotide – A review of its pharmacology and use in the treatment of chronic pain. Neuropsychiatr Dis Treat. 2007; 3(1): 69-85. http://dx.doi.org/10.2147/nedt.2007.3.1.69
Wallace MS, Rauck R, Fisher R, Charapata SG, Ellis D, Dissanayake S. Intrathecal ziconotide for severe chronic pain: safety and tolerability results of an open-label, longterm trial. Anesthesia & Analgesia 2008; 106: 628-37 http://dx.doi.org/10.1213/ane.0b013e3181606fad
Munday R, Thomas K, Gibbs R, Murphy C, Quilliam MA. Acute toxicities of saxitoxin, neosaxitoxin, decarbamoyl saxitoxin and gonyautoxins 1 & 4 and 2 & 3 to mice by various routes of administration. Toxicon. 2013; 76: 77-83. http://dx.doi.org/10.1016/j.toxicon.2013.09.013
Wylie MC, Johnson VM, Carpino E, Mullen K, Hauser K, Nedder A, et al. Respiratory, neuromuscular, and cardiovascular effects of neosaxitoxin in isoflurane-anesthetized sheep. Reg Anesth Pain Med. 2012; 37(2):152-8. http://dx.doi.org/10.1097/AAP.0b013e3182424566
García C, Barriga A, Díaz JC, Lagos M, Lagos N. Route of metabolization and detoxication of paralytic shellfish toxins in humans. Toxicon. 2010; 55(1): 135-44. http://dx.doi.org/10.1016/j.toxicon.2009.07.018
García C, del Carmen Bravo M, Lagos M, Lagos N. Paralytic shellfish poisoning: post-mortem analysis of tissue and body fluid samples from human victims in the Patagonia fjords Toxicon. 2004; 43(2): 149-58. http://dx.doi.org/10.1016/j.toxicon.2003.11.018
Zhang W, Tang Y. Combinatorial biosynthesis of natural products. J Med Chem. 2008; 51: 2629-2633. http://dx.doi.org/10.1021/jm701269v
