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Ralfinamide - Wikipedia

From Wikipedia, the free encyclopedia

Investigational analgesic drug

Pharmaceutical compound

Ralfinamide (INN; development codes NW-1029, FCE-26742A, and PNU-0154339E)[1] is a multimodal drug which is under investigation by Newron Pharmaceuticals for the treatment of neuropathic pain and other pain conditions such as post-operative dental pain.[2][3][4][5]

It has a relatively complex pharmacology, acting as a mixed voltage-gated sodium channel blocker (including Nav1.7),[2][3] N-type calcium channel blocker,[2][3] noncompetitive NMDA receptor antagonist,[6] and monoamine oxidase B inhibitor.[7][8]

As of 2020, it was in phase III clinical trials.[9][5][10] In 2010 it failed a phase II trial for lower back pain.[11] Encouraging Phase II results have been announced for neuropathic pain.[12]

  1. ^ Action A, ed. (22 July 2013). "Chapter 8: Therapies and Treatments". Pain: New Insights for the Healthcare Professional (2013 ed.). ScholarlyEditions. pp. 506–. ISBN 978-1-4816-6118-8.
  2. ^ a b c Gilron I (21 June 2012). "Drug Discovery for Neuropathic Pain". In Simpson DM, McArthur JC, Dworkin RH (eds.). Neuropathic Pain: Mechanisms, Diagnosis and Treatment. Oxford University Press. pp. 40–. ISBN 978-0-19-539470-2.
  3. ^ a b c Rodger IW, Lacouture PG (14 October 2010). "Overview: Novel Targets for New Analgesics". In Sinatra RS, Jahr JS, Watkins-Pitchford JM (eds.). The Essence of Analgesia and Analgesics. Cambridge University Press. pp. 436–. ISBN 978-1-139-49198-3.
  4. ^ Termin A, Martinborough E, Wilson D (17 December 2008). "Recent Advances in Voltage-Gated Sodium Chanel Blockers: Therapeutic Potential as Drug Targets in the CNS". Annual Reports in Medicinal Chemistry. Academic Press. pp. 55–. ISBN 978-0-08-092187-7.
  5. ^ a b Liu Y, Qin N (26 January 2010). "Pharacological Modulation of Ion Channels for the Treatment of Chronic Pain". In Lu C, Li AP (eds.). Enzyme Inhibition in Drug Discovery and Development: The Good and the Bad. John Wiley & Sons. pp. 689–. ISBN 978-0-470-53894-4.
  6. ^ Colombo E, Curatolo L, Caccia C, Salvati P, Faravelli L (2007). "344 Ralfinamide Acts Through Nmda Receptor Complex: A Central Role for Chronic Pain Treatment". European Journal of Pain. 11 (S1): S152 – S153. doi:10.1016/j.ejpain.2007.03.359. ISSN 1090-3801. S2CID 58186567.
  7. ^ Di Stefano AF, Radicioni MM, Rusca A (May 2013). "Pressor response to oral tyramine and monoamine oxidase inhibition during treatment with ralfinamide (NW-1029)". Neurotoxicity Research. 23 (4): 315–326. doi:10.1007/s12640-012-9344-5. PMID 22872464. S2CID 207442119.
  8. ^ Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G (14 April 2011). Rang & Dale's Pharmacology: with STUDENT CONSULT Online Access. Elsevier Health Sciences. pp. 2476–. ISBN 978-0-7020-4504-2.
  9. ^ "Ralfinamide - Newron Pharmaceuticals". Adis Insight.
  10. ^ Bowlby MR, Kaftan (9 December 2008). "Sodium Channel Blockers for the Treatment of Chronic Pain". In Gribkoff VK, Kaczmarek LK (eds.). Structure, Function and Modulation of Neuronal Voltage-Gated Ion Channels. John Wiley & Sons. pp. 377–. ISBN 978-0-470-42989-1.
  11. ^ "Newron reports SERENA trial top-line results for ralfinamide". Bloomberg. 6 May 2010. Archived from the original on 24 September 2015.
  12. ^ "Newron Announces Positive Results With Ralfinamide From Phase II Trial in Neuropathic Pain". PR Newswire. 26 October 2014. Archived from the original on 20 February 2015.
Analgesics

(

N02A

,

N02B

)

Opioids Opiates/opium Semisynthetic Synthetic Paracetamol-type NSAIDs Propionates Oxicams Acetates COX-2 inhibitors Fenamates Salicylates Pyrazolones Others Cannabinoids Ion channel
modulators Calcium blockers Sodium blockers Potassium openers Myorelaxants Others Neuropathic pain

and

fibromyalgia pharmacotherapies Monoaminergics Ion channel blockers Others Ion channel modulators Calcium VDCCsTooltip Voltage-dependent calcium channels Blockers Activators Potassium VGKCsTooltip Voltage-gated potassium channels Blockers Activators IRKsTooltip Inwardly rectifying potassium channel Blockers Activators KCaTooltip Calcium-activated potassium channel Blockers Activators K2PsTooltip Tandem pore domain potassium channel Blockers Activators Sodium VGSCsTooltip Voltage-gated sodium channels Blockers Activators ENaCTooltip Epithelial sodium channel Blockers Activators ASICsTooltip Acid-sensing ion channel Blockers Chloride CaCCsTooltip Calcium-activated chloride channel Blockers Activators CFTRTooltip Cystic fibrosis transmembrane conductance regulator Blockers Activators Unsorted Blockers Others TRPsTooltip Transient receptor potential channels LGICsTooltip Ligand gated ion channels See also: Receptor/signaling modulators • Transient receptor potential channel modulators Glutamate receptor modulators Ionotropic glutamate receptor modulators AMPARTooltip α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor KARTooltip Kainate receptor NMDARTooltip N-Methyl-D-aspartate receptor Metabotropic glutamate receptor modulators Group I mGluR1Tooltip Metabotropic glutamate receptor 1 mGluR5Tooltip Metabotropic glutamate receptor 5 Group II mGluR2Tooltip Metabotropic glutamate receptor 2 mGluR3Tooltip Metabotropic glutamate receptor 3 Group III mGluR4Tooltip Metabotropic glutamate receptor 4 mGluR6Tooltip Metabotropic glutamate receptor 6 mGluR7Tooltip Metabotropic glutamate receptor 7 mGluR8Tooltip Metabotropic glutamate receptor 8 See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Glutamate metabolism/transport modulators

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