Ralfinamide

Ralfinamide
Clinical data
ATC code	None;
Identifiers
	IUPAC name N2-{4-[(2-Fluorobenzyl)oxy]benzyl}-L-alaninamide;
CAS Number	133865-88-0;
PubChem CID	5745207;
ChemSpider	4676525;
UNII	3LPF0S0GVV;
ChEMBL	ChEMBL2107771;
CompTox Dashboard (EPA)	DTXSID70158406 ;
ECHA InfoCard	100.120.272
Chemical and physical data
Formula	C17H19FN2O2
Molar mass	302.349 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@@H](C(=O)N)NCc1ccc(cc1)OCc2ccccc2F;
	InChI InChI=1S/C17H19FN2O2/c1-12(17(19)21)20-10-13-6-8-15(9-7-13)22-11-14-4-2-3-5-16(14)18/h2-9,12,20H,10-11H2,1H3,(H2,19,21)/t12-/m0/s1; Key:BHJIBOFHEFDSAU-LBPRGKRZSA-N;

Ralfinamide (INN) (code names NW-1029, FCE-26742A, 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 Na_v1.7),^[2]^[3] N-type calcium channel blocker,^[2]^[3] noncompetitive NMDA receptor antagonist,^[6] and monoamine oxidase B inhibitor.^[7]^[8]

It has thus far progressed as far as phase IIb/phase III clinical trials.^[5]^[9] In 2010 it failed a phase II trial for lower back pain.^[10] Encouraging Phase II results have been announced for neuropathic pain.^[11]

References

^ 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.
^ ^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.
^ ^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.
^ 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.
^ ^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.
^ 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.
^ 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.
^ 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.
^ 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.
^ "Newron reports SERENA trial top-line results for ralfinamide". Bloomberg. 6 May 2010. Archived from the original on 24 September 2015.
^ "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.

External links

Ralfinamide - Newron Pharmaceuticals Archived 2015-01-03 at the Wayback Machine

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[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.

[SimpsonMcArthur2012-2] 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.

[SinatraJahr2010-3] 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.

[LuLi2010-5] 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.

[ColomboCuratolo2007-6] 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.

[pmid22872464-7] 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.

[RangDale2011-8] 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.

[GribkoffKaczmarek2008-9] 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.

[10] "Newron reports SERENA trial top-line results for ralfinamide". Bloomberg. 6 May 2010. Archived from the original on 24 September 2015.

[11] "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.

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v t e Neuropathic pain and fibromyalgia pharmacotherapies
Monoaminergics	SNRIsTooltip Serotonin–norepinephrine reuptake inhibitor (e.g., duloxetine, milnacipran) TCAsTooltip Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, dosulepin) Opioid MRIsTooltip monoamine reuptake inhibitors (e.g., tapentadol, tramadol)
Ion channel blockers	Anticonvulsants (e.g., gabapentin, pregabalin, mirogabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine) Local anesthetics (e.g., lidocaine) Mexiletine TCAsTooltip Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, desipramine) Ziconotide
Others	Alpha lipoic acid Benfotiamine Botulinum toxin A Bupropion Cannabinoids (e.g., cannabis, dronabinol, nabilone) NMDA receptor antagonists (e.g., ketamine, dextromethorphan, methadone) Opioids (e.g., hydrocodone, morphine, oxycodone, methadone, buprenorphine, tramadol, tapentadol) Sodium oxybate (GHB)

See also

References

External links