586
Views
44
CrossRef citations to date
0
Altmetric
Review

Investigational sigma-1 receptor antagonists for the treatment of pain

, &

Bibliography

  • Kissin I. The development of new analgesics over the past 50 years: a lack of real breakthrough drugs. Anesth Analg 2010;110(3):780-9
  • Cobos EJ, Entrena JM, Nieto FR, et al. Pharmacology and therapeutic potential of sigma(1) receptor ligands. Curr Neuropharmacol 2008;6(4):344-66
  • Maurice T, Su TP. The pharmacology of sigma-1 receptors. Pharmacol Ther 2009;124(2):195-206
  • Su TP, Hayashi T, Maurice T, et al. The sigma-1 receptor chaperone as an inter-organelle signaling modulator. Trends Pharmacol Sci 2010;31(12):557-66
  • Zamanillo D, Romero L, Merlos M, Vela JM. Sigma 1 receptor: a new therapeutic target for pain. Eur J Pharmacol 2013;716(1-3):78-93
  • Sánchez-Fernández C, Montilla-García Á, González-Cano R, et al. Modulation of peripheral μ-opioid analgesia by σ1 receptors. J Pharmacol Exp Ther 2014;348(1):32-45
  • Roh DH, Kim HW, Yoon SY, et al. Intrathecal injection of the sigma(1) receptor antagonist BD1047 blocks both mechanical allodynia and increases in spinal NR1 expression during the induction phase of rodent neuropathic pain. Anesthesiology 2008;109(5):879-89
  • Vidal-Torres A, de la Puente B, Rocasalbas M, et al. Sigma-1 receptor antagonism as opioid adjuvant strategy: enhancement of opioid antinociception without increasing adverse effects. Eur J Pharmacol 2013;711(1-3):63-72
  • Chien CC, Pasternak GW. Functional antagonism of morphine analgesia by (+)-pentazocine: evidence for an anti-opioid sigma 1 system. Eur J Pharmacol 1993;250(1):R7-8
  • Chien CC, Pasternak GW. Selective antagonism of opioid analgesia by a sigma system. J Pharmacol Exp Ther 1994;271(3):1583-90
  • Chien CC, Pasternak GW. Sigma antagonists potentiate opioid analgesia in rats. Neurosci Lett 1995;190(2):137-9
  • King M, Pan YX, Mei J, et al. Enhanced kappa-opioid receptor-mediated analgesia by antisense targeting the sigma1 receptor. Eur J Pharmacol 1997;331(1):R5-6
  • Mei J, Pasternak GW. Sigma1 receptor modulation of opioid analgesia in the mouse. J Pharmacol Exp Ther 2002;300(3):1070-4
  • Kim FJ, Kovalyshyn I, Burgman M, et al. Sigma 1 receptor modulation of G-protein-coupled receptor signaling: potentiation of opioid transduction independent from receptor binding. Mol Pharmacol 2010;77(4):695-703
  • Cendán CM, Pujalte JM, Portillo-Salido E, et al. Formalin-induced pain is reduced in sigma(1) receptor knockout mice. Eur J Pharmacol 2005;511(1):73-4
  • Cendán CM, Pujalte JM, Portillo-Salido E, et al. Antinociceptive effects of haloperidol and its metabolites in the formalin test in mice. Psychopharmacology (Berl) 2005;182(4):485-93
  • Entrena JM, Cobos EJ, Nieto FR, et al. Sigma-1 receptors are essential for capsaicin-induced mechanical hypersensitivity: studies with selective sigma-1 ligands and sigma-1 knockout mice. Pain 2009;143(3):252-6
  • Entrena JM, Cobos EJ, Nieto FR, et al. Antagonism by haloperidol and its metabolites of mechanical hypersensitivity induced by intraplantar capsaicin in mice: role of sigma-1 receptors. Psychopharmacology (Berl) 2009;205(1):21-33
  • Kim HW, Kwon YB, Roh DH, et al. Intrathecal treatment with sigma1 receptor antagonists reduces formalin-induced phosphorylation of NMDA receptor subunit 1 and the second phase of formalin test in mice. Br J Pharmacol 2006;148(4):490-8
  • Kim HW, Roh DH, Yoon SY, et al. Activation of the spinal sigma-1 receptor enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NR1 subunit in mice. Br J Pharmacol 2008;154(5):1125-34
  • de la Puente B, Nadal X, Portillo-Salido E, et al. Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury. Pain 2009;145(3):294-303
  • Romero L, Zamanillo D, Nadal X, et al. Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization. Br J Pharmacol 2012;166(8):2289-306
  • Mazo I, Roza C, Zamanillo D, et al. Effects of centrally acting analgesics on spinal segmental reflexes and wind-up. Eur J Pain 2014; Epub ahead of print
  • Hayashi T, Tsai SY, Mori T, et al. Targeting ligand-operated chaperone sigma-1 receptors in the treatment of neuropsychiatric disorders. Expert Opin Ther Targets 2011;15(5):557-77
  • Zamanillo D, Portillo-Salido E, Vela JM, et al. Therapeutic targets: modulation, inhibition, and activation. In: Botana LM, Loza M, editors. Sigma 1 receptor chaperone: pharmacology and therapeutic perspectives. John Wiley & Sons, Inc, Hoboken, NJ, USA; 2012. p. 225-78
  • Collina S, Gaggeri R, Marra A, et al. Sigma receptor modulators: a patent review. Expert Opin Ther Pat 2013;23(5):597-613
  • Tsai SY, Pokrass MJ, Klauer NR, et al. Sigma-1 receptor chaperones in neurodegenerative and psychiatric disorders. Expert Opin Ther Targets 2014;18(12):1461-76
  • Almansa C, Vela JM. Selective sigma-1-receptor antagonists for the treatment of pain. Future Med Chem 2014;6(10):1179-99
  • Sánchez-Fernández C, Nieto FR, González-Cano R, et al. Potentiation of morphine-induced mechanical antinociception by σ2 receptor inhibition: role of peripheral σ2 receptors. Neuropharmacology 2013;70:348-58
  • Moon JY, Roh DH, Yoon SY, et al. Sigma-1 receptor-mediated increase in spinal p38 MAPK phosphorylation leads to the induction of mechanical allodynia in mice and neuropathic rats. Exp Neurol 2013;247:383-91
  • Moon JY, Roh DH, Yoon SY, et al. σ1 receptors activate astrocytes via p38 MAPK phosphorylation leading to the development of mechanical allodynia in a mouse model of neuropathic pain. Br J Pharmacol 2014;171(24):5881-97
  • Choi SR, Roh DH, Yoon SY, et al. Spinal sigma-1 receptors activate NADPH oxidase 2 leading to the induction of pain hypersensitivity in mice and mechanical allodynia in neuropathic rats. Pharmacol Res 2013;74:56-67
  • Kwon YB, Jeong YC, Kwon JK, et al. The antinociceptive effect of sigma-1 receptor antagonist, BD1047, in a capsaicin induced headache model in rats. Korean J Physiol Pharmacol 2009;13(6):425-9
  • Roh DH, Yoon SY. Sigma-1 receptor antagonist, BD1047 reduces nociceptive responses and phosphorylation of p38 MAPK in mice orofacial formalin model. Biol Pharm Bull 2014;37(1):145-51
  • Son JS, Kwon YB. Sigma-1 receptor antagonist BD1047 reduces allodynia and spinal ERK phosphorylation following chronic compression of dorsal root ganglion in rats. Korean J Physiol Pharmacol 2010;14(6):359-64
  • Díaz JL, Zamanillo D, Corbera J, et al. Selective sigma-1 (sigma1) receptor antagonists: emerging target for the treatment of neuropathic pain. Cent Nerv Syst Agents Med Chem 2009;9(3):172-83
  • Nieto FR, Cendán CM, Sánchez-Fernández C, et al. Role of sigma-1 receptors in paclitaxel-induced neuropathic pain in mice. J Pain 2012;13(11):1107-21
  • González-Cano R, Merlos M, Baeyens JM, et al. σ1 receptors are involved in the visceral pain induced by intracolonic administration of capsaicin in mice. Anesthesiology 2013;118(3):691-700
  • Tejada MA, Montilla-García A, Sánchez-Fernández C, et al. Sigma-1 receptor inhibition reverses acute inflammatory hyperalgesia in mice: role of peripheral sigma-1 receptors. Psychopharmacology (Berl) 2014;231(19):3855-69
  • Kotagale NR, Shirbhate SH, Shukla P, Ugale RR. Agmatine attenuates neuropathic pain in sciatic nerve ligated rats: modulation by hippocampal sigma receptors. Eur J Pharmacol 2013;714(1-3):424-31
  • Leppert W, Okulicz-Kozaryn I, Kaminska E, et al. Analgesic effects of morphine in combination with adjuvant drugs in rats. Pharmacology 2014;94(5-6):207-13
  • King MA, Rossi GC, Chang AH, et al. Spinal analgesic activity of orphanin FQ/nociceptin and its fragments. Neurosci Lett 1997;223(2):113-16
  • Mei J, Pasternak GW. Modulation of brainstem opiate analgesia in the rat by sigma 1 receptors: a microinjection study. J Pharmacol Exp Ther 2007;322(3):1278-85
  • Becker A, Grecksch G, Zernig G, et al. Haloperidol and risperidone have specific effects on altered pain sensitivity in the ketamine model of schizophrenia. Psychopharmacology (Berl) 2009;202(4):579-87
  • Yang C, Chen Y, Tang L, et al. Haloperidol disrupts opioid-antinociceptive tolerance and physical dependence. J Pharmacol Exp Ther 2011;338(1):164-72
  • Okulicz-Kozaryn I, Leppert W, Mikolajczak P, Kaminska E. Analgesic effects of tramadol in combination with adjuvant drugs: an experimental study in rats. Pharmacology 2013;91(1-2):7-11
  • Stevenson GW, Cormier J, Mercer H, et al. Targeting pain-depressed behaviors in preclinical assays of pain and analgesia: drug effects on acetic acid-depressed locomotor activity in ICR mice. Life Sci 2009;85(7-8):309-15
  • Farriols C, Ferrández O, Planas J, et al. Changes in the prescription of psychotropic drugs in the palliative care of advanced cancer patients over a seven-year period. J Pain Symptom Manage 2012;43(5):945-52
  • Colclough G, McLarney JT, Sloan PA, et al. Epidural haloperidol enhances epidural morphine analgesia: three case reports. J Opioid Manag 2008;4(3):163-6
  • Benevides ML, Oliveira Sde S, Aguilar-Nascimento JE. Combination of haloperidol, dexamethasone, and ondansetron reduces nausea and pain intensity and morphine consumption after laparoscopic sleeve gastrectomy. Braz J Anesthesiol 2013;63(5):404-9
  • Salpeter SR, Buckley JS, Buckley NS, Bruera E. The use of very-low-dose methadone and haloperidol for pain control in the hospital setting: a preliminary report. J Palliat Med 2015;18(2):114-19
  • Salpeter SR, Buckley JS, Bruera E. The use of very-low-dose methadone for palliative pain control and the prevention of opioid hyperalgesia. J Palliat Med 2013;16(6):616-22
  • Gear RW, Lee JS, Miaskowski C, et al. Neuroleptics antagonize nalbuphine antianalgesia. J Pain 2006;7(3):187-91
  • Daw JL, Cohen-Cole SA. Haloperidol analgesia. South Med J 1981;74(3):364-5
  • Monzillo PH, Nemoto PH, Costa AR, et al. Acute treatment of migraine in emergency room: comparative study between dexametasone and haloperidol. Preliminary results. Arq Neuropsiquiatr 2004;62(2B):513-18
  • Honkaniemi J, Liimatainen S, Rainesalo S, et al. Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study. Headache 2006;46(5):781-7
  • Marrazzo A, Parenti C, Scavo V, et al. In vivo evaluation of (+)-MR200 as a new selective sigma ligand modulating MOP, DOP and KOP supraspinal analgesia. Life Sci 2006;78(21):2449-53
  • Parenti C, Marrazzo A, Aricò G, et al. The antagonistic effect of the sigma 1 receptor ligand (+)-MR200 on persistent pain induced by inflammation. Inflamm Res 2014;63(3):231-7
  • Marrazzo A, Cobos EJ, Parenti C, et al. Novel potent and selective σ ligands: Evaluation of their agonist and antagonist properties. J Med Chem 2011;54(10):3669-73
  • Parenti C, Marrazzo A, Aricò G, et al. Effects of a selective sigma 1 antagonist compound on inflammatory pain. Inflammation 2013;37(1):261-6
  • Utech T, Köhler J, Buschmann H, et al. Synthesis and pharmacological evaluation of a potent and selective σ1 receptor antagonist with high antiallodynic activity. Arch Pharm (Weinheim) 2011;344(7):415-21
  • Utech T, Köhler J, Wünsch B. Synthesis of 4-(aminoalkyl) substituted 1,3-dioxanes as potent NMDA and σ receptor antagonists. Eur J Med Chem 2011;46(6):2157-69
  • Wiese C, Grosse Maestrup E, et al. Pharmacological and metabolic characterisation of the potent sigma1 receptor ligand 1’-benzyl-3-methoxy-3H-spiro[[2]benzofuran-1,4’-piperidine]. J Pharm Pharmacol 2009;61(5):631-40
  • Schläger T, Schepmann D, Lehmkuhl K, et al. Combination of two pharmacophoric systems: synthesis and pharmacological evaluation of spirocyclic pyranopyrazoles with high σ1 receptor affinity. J Med Chem 2011;54(19):6704-13
  • Oberdorf C, Schepmann D, Vela JM, et al. Thiophene bioisosteres of spirocyclic sigma receptor ligands. 1. N-substituted spiro[piperidine-4,4’-thieno[3,2-c]pyrans]. J Med Chem 2008;51(20):6531-7
  • Oberdorf C, Schepmann D, Vela JM, et al. Thiophene bioisosteres of spirocyclic σ receptor ligands: relationships between substitution pattern and σ receptor affinity. J Med Chem 2012;55(11):5350-60
  • Riganas S, Papanastasiou I, Foscolos GB, et al. New adamantane phenylalkylamines with σ-receptor binding affinity and anticancer activity, associated with putative antagonism of neuropathic pain. J Med Chem 2012;55(22):10241-61
  • Riganas S, Papanastasiou I, Foscolos GB, et al. New adamantane derivatives with sigma affinity and antiproliferative activity. Med Chem 2012;8(4):569-86
  • Poster communication: 8th AFMC Int Med Chem Symp Nov 29-Dec 2 Tokyo Abst 2P-132 (2011)
  • Mochida Pharmaceutical Co. Ltd. Therapeutic agent for pain. WO118307; 2006
  • Lan Y, Chen Y, Xu X, et al. Synthesis and biological evaluation of a novel sigma-1 receptor antagonist based on 3,4-dihydro-2(1H)-quinolinone scaffold as a potential analgesic. Eur J Med Chem 2014;79:216-30
  • Lan Y, Chen Y, Cao X, et al. Synthesis and biological evaluation of novel sigma-1 receptor antagonists based on pyrimidine scaffold as agents for treating neuropathic pain. J Med Chem 2014;57(24):10404-23
  • Laboratorios del Dr. Esteve SA. 2-(1-Phenyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)-ethylamine derivatives useful as sigma receptor inhibitors. WO072791; 2012
  • Laboratorios del Dr. Esteve, S.A. Pyrazolo[3,4-d]pyrimidine compounds, their preparation and use as sigma ligands. WO010950; 2013
  • Diaz JL, Corbera J, Cuberes R, et al. Synthesis and SAR of a new series of pyrazolo[3,4-d]pyrimidines as sigma-1 receptor antagonists. XXIII International Symposium on Medicinal Chemistry; 2014, Lisbon
  • Laboratorios del Dr. Esteve, S.A. Substituted pyrazolo[3,4-d] pyrimidine compounds, their preparation and use as sigma ligands. WO076170; 2014
  • Alcalde E, Mesquida N, Paloma L, et al. Conversion of 5-HT6 serotonin receptor ligands to sigma-1-preferring agents. XXIII International Symposium on Medicinal Chemistry; 2014, Lisbon
  • Laboratorios del Dr. Esteve SA. New indene derivatives, their preparation and use as medicaments. WO006071; 2014
  • Mesquida N, Alcalde E, Paloma L, et al. Targeting the sigma-1 receptor: indene-based scaffolds as potent and selective ligands. XXIII International Symposium on Medicinal Chemistry; 2014, Lisbon
  • Laboratorios del Dr. Esteve, S.A. Pyrazole compounds as sigma receptor inhibitors. WO147910; 2011
  • Laboratorios del Dr. Esteve, S.A. Substituted pyrazolo[1,5-a]pyridines, their preparation and use as medicaments. WO124341; 2013
  • Laboratorios del Dr. Esteve, S.A. 1,2,3-Triazole-4-amine derivatives for the treatment of sigma receptor diseases or disorders. WO106622; 2014
  • Díaz JL, Christmann U, Fernández A, et al. 4-Aminotriazole sigma-1 receptor antagonists derived from a scaffold hopping approach over E-52862. XXIII International Symposium on Medicinal Chemistry; 2014, Lisbon
  • Díaz JL, Christmann U, Fernández A, et al. Synthesis and Structure-Activity Relationship (SAR) Study of a New Series of Selective σ1 Receptor Ligands for the Treatment of Pain: 4-Aminotriazoles. J Med Chem 2015;58(5):2441-51
  • Laboratorios del Dr. Esteve, S.A. Tricyclic triazolic compounds. WO170494; 2014
  • Laboratorios del Dr. Esteve, S.A. Tricyclic triazolic compounds. WO071657; 2009
  • Díaz JL, Christmann U, Fernández A, et al. Synthesis and biological evaluation of a new series of hexahydro-2H-pyrano[3,2-c]quinolines as novel selective σ1 receptor ligands. J Med Chem 2013;56(9):3656-65
  • Laboratorios del Dr. Esteve, S.A. Substituted furano and pyranoquinolines, their preparation and use as medicaments. WO110698; 2013
  • Laboratorios del Dr. Esteve, S.A. Imidazo[2,1-b]thiazole derivatives, their preparation and use as medicaments. WO006130; 2014
  • Laboratorios del Dr. Esteve, S.A. Pyrazino[1,2-a]indole compounds, their preparation and use in medicaments. WO173903; 2014
  • Laboratorios del Dr. Esteve, S.A. Pyrazino[1,2-a]indole compounds, their preparation and use in medicaments. WO173901; 2014
  • Rajagopalan R, Bandyopadhyaya A, Rajagopalan DR, Rajagopalan P. The synthesis and comparative receptor binding affinities of novel, isomeric pyridoindolobenzazepine scaffolds. Bioorg Med Chem Lett 2014;24(2):576-9
  • Daya Drug Discoveries Inc. Pentacyclic pyridoindolobenz[b,d]azepine derivatives and uses thereof. WO137848; 2014
  • Rajagopalan P, Tracey H, Chen Z, et al. DDD-028: a potent potential non-opioid, non-cannabinoid analgesic for neuropathic and inflammatory pain. Bioorg Med Chem Lett 2014;24(14):3088-91
  • Hasebein P, Frehland B, Schepmann D, et al. Synthesis, σ receptor affinity, and pharmacological evaluation of 5-phenylsulfanyl- and 5-benzyl-substituted tetrahydro-2-benzazepines. ChemMedChem 2014;9(8):1697-703
  • Westfälische Wilhems Universität Münster. Benzazepines and benzazocines as sigma receptor ligands. WO012812; 2010
  • Hasebein P, Frehland B, Lehmkuhl K, et al. Synthesis and pharmacological evaluation of like- and unlike-configured tetrahydro-2-benzazepines with the α-substituted benzyl moiety in the 5-position. Org Biomol Chem 2014;12(29):5407-26
  • Díaz JL, Cuberes R, Berrocal J, et al. Synthesis and biological evaluation of the 1-arylpyrazole class of σ(1) receptor antagonists: identification of 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862). J Med Chem 2012;55(19):8211-24
  • Abadias M, Escriche M, Vaqué A, et al. Safety, tolerability and pharmacokinetics of single and multiple doses of a novel sigma-1 receptor antagonist in three randomized phase I studies. Br J Clin Pharmacol 2013;75(1):103-17
  • Mitsubishi Pharma Corp. Cyclic amide derivatives. US7166617B2; 2007
  • Cyrenaic Pharmaceuticals Inc. Methods of use of cyclic amide derivatives for the treatment of schizophrenia. WO012542; 2012
  • Villard V, Espallergues J, Keller E, et al. Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma 1 (σ1) ligand ANAVEX2-73, a novel aminotetrahydrofuran derivative. J Psychopharmacol 2011;25(8):1101-17
  • Anavex doses first Alzheimer’s patient in Phase IIa trial of Anavez 2-73 and Anavex-Plus. New York, Anavex Life Sciences Corp. 2015. Available from: http://www.anavex.com/?post_type=news&p=1372 [Last accessed 22 February 2015]
  • M’s Science Corp. Sigma ligands for neuronal regeneration and functional recovery. WO053580; 2007
  • Urfer R, Moebius HJ, Skoloudik D, et al. Phase II trial of the Sigma-1 receptor agonist cutamesine (SA4503) for recovery enhancement after acute ischemic stroke. Stroke 2014;45(11):3304-10
  • Central Nervous System (CNS): Cutamesine(SA4503). M’s Science Corporation, Research & Development. Chuo-ku Kobe, Japan: M’s Science Corporation. 2015. Available from: http://www.m-sci.com/e/kaihatsu/msc1.html [Last accessed 22 February 2015]
  • Vidal-Torres A, Fernández-Pastor B, Carceller A, et al. Effects of the selective sigma-1 receptor antagonist S1RA on formalin-induced pain behavior and neurotransmitter release in the spinal cord in rats. J Neurochem 2014;129(3):484-94
  • Paniagua N, Girón R, Goicoechea C, et al. Blockade of sigma 1 receptors and the Development of sensory signs of diabetic neuropathy in rats. 15th World Congress on Pain, IASP; Buenos Aires: 2014
  • Bura AS, Guegan T, Zamanillo D, et al. Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain. Eur J Pain 2013;17(6):832-43
  • Gris G, Merlos M, Vela JM, et al. S1RA, a selective sigma-1 receptor antagonist, inhibits inflammatory pain in the carrageenan and complete Freund’s adjuvant models in mice. Behav Pharmacol 2014;25(3):226-35
  • Gris G, Portillo-Salido E, Vela JM, et al. Role of sigma-1 receptor (σ1R) in postoperative pain in mice. 15th World Congress on Pain, IASP; Buenos Aires: 2014
  • Vidal-Torres A, Fernández-Pastor B, Carceller A, et al. Supraspinal and peripheral but not intrathecal sigma-1 receptor blockade by the selective sigma-1 receptor antagonist E-52862 enhances morphine antinociception. 15th World Congress on Pain, IASP; Buenos Aires: 2014
  • Turk DC, Wilson HD, Cahana A. Treatment of chronic non-cancer pain. Lancet 2011;377(9784):2226-35
  • Labianca R, Sarzi-Puttini P, Zuccaro SM, et al. Adverse effects associated with non-opioid and opioid treatment in patients with chronic pain. Clin Drug Investig 2012;32(Suppl 1):53-63

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.