title: Dynorphin A analogs for the treatment of chronic neuropathic pain.
abstract: Chronic pain is one of the most ubiquitous diseases in the world, but treatment is difficult with conventional methods, due to undesirable side effects of treatments and unknown mechanisms of pathological pain states. The endogenous peptide, dynorphin A has long been established as a target for the treatment of pain. Interestingly, this unique peptide has both inhibitory (opioid in nature) and excitatory activities (nonopioid) in the CNS. Both of these effects have been found to play a role in pain and much work has been done to develop therapeutics to enhance the inhibitory effects. Here we will review the dynorphin A compounds that have been designed for the modulation of pain and will discuss where the field stands today.
authors.affiliation: Department of Chemistry & Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Hall
authors.affiliation: Department of Chemistry & Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Yeon Sun
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Chemistry & Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D002908:Chronic Disease; D004399:Dynorphins / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D009437:Neuralgia / Q000188:drug therapy* / Q000473:pathology; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000627:therapeutic use; D018002:Receptors, Bradykinin / Q000737:chemistry / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D018712:Analgesics, Non-Narcotic; D018377:Neurotransmitter Agents; D018002:Receptors, Bradykinin; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D004399:Dynorphins
references.citation: Neurosci Lett. 1990 Mar 2;110(1-2):113-7
references.pmid: 1970139
references.citation: Epilepsy Behav. 2011 Dec;22(4):617-40
references.pmid: 22056342
references.citation: Br J Pharmacol. 2001 Apr;132(8):1948-56
references.pmid: 11309268
references.citation: J Pharmacol Exp Ther. 1999 Apr;289(1):378-85
references.pmid: 10087027
references.citation: J Med Chem. 1990 Jan;33(1):206-12
references.pmid: 1967312
references.citation: Palliat Med. 2005 Sep;19(6):477-84
references.pmid: 16218160
references.citation: J Neurophysiol. 2006 Dec;96(6):3465-73
references.pmid: 17005613
references.citation: Peptides. 1980 Winter;1(4):341-5
references.pmid: 7301637
references.citation: J Neurophysiol. 2000 May;83(5):2610-5
references.pmid: 10805661
references.citation: Eur J Pharmacol. 1994 Dec 12;271(1):241-4
references.pmid: 7698209
references.citation: J Pharmacol Exp Ther. 1998 Jul;286(1):136-41
references.pmid: 9655852
references.citation: Proc Natl Acad Sci U S A. 1979 Dec;76(12):6666-70
references.pmid: 230519
references.citation: Neuropharmacology. 2014 Nov;86:301-10
references.pmid: 25172308
references.citation: Pain. 2000 May;86(1-2):185-94
references.pmid: 10779675
references.citation: Neuromodulation. 2013 Nov-Dec;16(6):576-81; discussion 582
references.pmid: 23205907
references.citation: Pain. 1996 Dec;68(2-3):275-81
references.pmid: 9121815
references.citation: J Neurosci. 1992 Feb;12(2):425-9
references.pmid: 1346803
references.citation: Ann N Y Acad Sci. 2000;909:104-32
references.pmid: 10911926
references.citation: Bioorg Med Chem Lett. 2015 Jan 1;25(1):30-3
references.pmid: 25434001
references.citation: J Neurosci. 2001 Jan 1;21(1):279-86
references.pmid: 11150345
references.citation: Br J Pharmacol. 1984 Feb;81(2):271-6
references.pmid: 6142741
references.citation: J Med Chem. 1993 Mar 19;36(6):750-7
references.pmid: 8096246
references.citation: Peptides. 1987 Jul-Aug;8(4):701-7
references.pmid: 2888101
references.citation: J Med Chem. 2014 Aug 14;57(15):6383-92
references.pmid: 24978316
references.citation: J Subst Abuse Treat. 2000 Apr;18(3):277-81
references.pmid: 10742642
references.citation: Eur J Pharmacol. 2004 Oct 6;501(1-3):111-9
references.pmid: 15464069
references.citation: J Pain Symptom Manage. 1994 Oct;9(7):442-5
references.pmid: 7822883
references.citation: J Med Chem. 1995 Feb 17;38(4):585-6
references.pmid: 7861405
references.citation: J Neurosci. 2004 Feb 11;24(6):1451-8
references.pmid: 14960618
references.citation: J Pharmacol Exp Ther. 1994 Apr;269(1):358-66
references.pmid: 7909561
references.citation: Science. 1982 Dec 10;218(4577):1136-8
references.pmid: 6128791
references.citation: N Engl J Med. 1988 Jun 30;318(26):1728-33
references.pmid: 3374545
references.citation: Proc Natl Acad Sci U S A. 1981 Nov;78(11):7219-23
references.pmid: 6118870
references.citation: Eur J Pharmacol. 1989 Oct 24;170(1-2):125-6
references.pmid: 2575525
references.citation: Brain Res. 1991 Mar 15;543(2):322-6
references.pmid: 1676332
references.citation: J Pharmacol Exp Ther. 2007 Dec;323(3):838-45
references.pmid: 17823306
references.citation: Eur J Pharmacol. 1986 May 27;124(3):343-7
references.pmid: 2426121
references.citation: Am J Addict. 2009 Jul-Aug;18(4):272-6
references.pmid: 19444730
references.citation: Brain Res. 2010 Feb 16;1314:44-55
references.pmid: 19716811
references.citation: J Med Chem. 2003 Apr 10;46(8):1279-82
references.pmid: 12672226
references.citation: AAPS J. 2009 Jun;11(2):312-22
references.pmid: 19430912
references.citation: Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7006-10
references.pmid: 7624359
references.citation: Eur J Pharmacol. 2007 Aug 13;569(1-2):84-9
references.pmid: 17568579
references.citation: Neuropeptides. 1983 Jan;3(3):233-40
references.pmid: 16229165
references.citation: Brain Res Rev. 2009 Dec 11;62(1):127-46
references.pmid: 19804796
references.citation: J Pharmacol Exp Ther. 1997 Aug;282(2):633-8
references.pmid: 9262324
references.citation: Nat Clin Pract Neurol. 2006 Feb;2(2):95-106
references.pmid: 16932531
references.citation: Br J Pharmacol. 1993 Dec;110(4):1369-74
references.pmid: 7508324
references.citation: Nat Neurosci. 2006 Dec;9(12):1534-40
references.pmid: 17115041
references.citation: Brain Res. 1988 Mar 8;443(1-2):329-32
references.pmid: 2896056
references.citation: Trends Neurosci. 1992 Mar;15(3):96-103
references.pmid: 1373925
references.citation: Int J Neuropsychopharmacol. 2008 Mar;11(2):243-7
references.pmid: 17897484
references.citation: Pharmacol Ther. 2009 Sep;123(3):353-70
references.pmid: 19481570
references.citation: J Pharmacol Exp Ther. 1990 Mar;252(3):1247-54
references.pmid: 1969472
references.citation: Agents Actions. 1985 Apr;16(3-4):269-72
references.pmid: 2409776
references.citation: Science. 1986 Aug 15;233(4765):774-6
references.pmid: 3016896
references.citation: Life Sci. 1982 Oct 18-25;31(16-17):1821-4
references.pmid: 6130448
references.citation: Bioorg Med Chem. 1998 Jan;6(1):57-62
references.pmid: 9502105
references.citation: Ann Pharmacother. 2006 Jul-Aug;40(7-8):1293-300
references.pmid: 16849624
references.citation: J Pain. 2008 Dec;9(12):1096-105
references.pmid: 18976961
references.citation: Life Sci. 1983;33 Suppl 1:661-4
references.pmid: 6141507
references.citation: JAMA. 2003 Nov 12;290(18):2443-54
references.pmid: 14612481
references.citation: Proc Natl Acad Sci U S A. 1981 Oct;78(10):6543-7
references.pmid: 6118865
references.citation: Mol Pharmacol. 1994 Jan;45(1):1-8
references.pmid: 8302267
references.citation: Annu Rev Pharmacol Toxicol. 1991;31:129-62
references.pmid: 2064371
references.citation: J Am Soc Mass Spectrom. 2001 Jan;12(1):88-96
references.pmid: 11142364
references.citation: Life Sci. 2004 Jun 4;75(3):257-70
references.pmid: 15135648
references.citation: Trends Pharmacol Sci. 1990 Feb;11(2):70-6
references.pmid: 2156363
references.citation: Science. 1982 Jan 22;215(4531):413-5
references.pmid: 6120570
references.citation: Eur J Pharmacol. 1984 Jul 13;102(2):213-27
references.pmid: 6148248
references.citation: J Proteome Res. 2006 Apr;5(4):1017-23
references.pmid: 16602711
references.citation: J Med Chem. 1990 Jul;33(7):1874-9
references.pmid: 1972964
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18396-401
references.pmid: 19841255
references.citation: Neuroreport. 1998 Jun 1;9(8):1777-81
references.pmid: 9665599
references.citation: Proc Natl Acad Sci U S A. 1988 Jun;85(11):4061-5
references.pmid: 2836869
references.citation: Neuropsychiatr Dis Treat. 2007 Feb;3(1):69-85
references.pmid: 19300539
references.citation: J Mol Med (Berl). 2001 Jun;79(5-6):226-42
references.pmid: 11485015
references.citation: Arch Biochem Biophys. 1982 Oct 1;218(1):329-34
references.pmid: 7149738
references.citation: J Pharmacol Exp Ther. 1989 Nov;251(2):461-8
references.pmid: 2553920
references.citation: Cochrane Database Syst Rev. 2009 Jul 08;(3):CD007076
references.pmid: 19588419
references.citation: J Med Chem. 1994 Nov 11;37(23):3910-7
references.pmid: 7966152
references.citation: Pharmacol Ther. 2007 Nov;116(2):306-21
references.pmid: 17868902
references.citation: Mol Pharmacol. 2012 Feb;81(2):264-72
references.pmid: 22072818
references.citation: Bioorg Med Chem Lett. 2014 Nov 1;24(21):4976-9
references.pmid: 25282551
references.citation: Pain. 2010 Sep;150(3):573-81
references.pmid: 20705215
references.citation: Eur J Pharmacol. 1984 Nov 13;106(2):457-8
references.pmid: 6152222
references.citation: Neuropeptides. 1985 Feb;5(4-6):423-4
references.pmid: 2860600
references.citation: J Med Chem. 2005 Jul 14;48(14):4500-3
references.pmid: 15999987
references.citation: J Pharmacol Exp Ther. 1985 Jan;232(1):27-32
references.pmid: 2856940
references.citation: J Med Chem. 1997 Aug 15;40(17):2733-9
references.pmid: 9276018
references.citation: J Am Chem Soc. 2014 May 7;136(18):6608-16
references.pmid: 24742335
references.citation: Am Fam Physician. 2005 Mar 1;71(5):913-8
references.pmid: 15768621
references.citation: Int J Pept Protein Res. 1993 Nov;42(5):411-9
references.pmid: 7906258
references.citation: Adv Exp Med Biol. 2003;521:148-60
references.pmid: 12617572
references.citation: Psychopharmacology (Berl). 2010 Jun;210(2):137-47
references.pmid: 20401607
references.citation: J Med Chem. 2002 Dec 19;45(26):5617-9
references.pmid: 12477343
references.citation: J Proteome Res. 2006 Jan;5(1):122-6
references.pmid: 16396502
references.citation: J Med Chem. 2000 Jul 13;43(14):2698-702
references.pmid: 10893307
references.citation: Basic Clin Pharmacol Toxicol. 2005 Jun;96(6):399-409
references.pmid: 15910402
references.citation: J Pharmacol Exp Ther. 1999 Nov;291(2):760-5
references.pmid: 10525097
references.citation: J Biol Chem. 1997 Oct 24;272(43):26959-64
references.pmid: 9341132
references.citation: Nature. 1997 Sep 25;389(6649):382-5
references.pmid: 9311779
references.citation: Neuroscientist. 2004 Jun;10(3):221-34
references.pmid: 15155061
references.citation: Neuroscience. 2004;126(4):1043-52
references.pmid: 15207337
references.citation: Nature. 1999 Jun 17;399(6737):697-700
references.pmid: 10385123
references.citation: Biochem Biophys Res Commun. 1992 Apr 15;184(1):260-8
references.pmid: 1314587
references.citation: Gastroenterology. 2006 Jun;130(7):2155-64
references.pmid: 16762636
references.citation: Pain. 2009 Feb;141(3):283-91
references.pmid: 19147290
references.citation: J Neurosci. 2001 Mar 1;21(5):1779-86
references.pmid: 11222667
references.citation: Brain Res. 1992 Sep 18;591(1):176-80
references.pmid: 1359918
references.citation: J Med Chem. 2001 Sep 13;44(19):3048-53
references.pmid: 11543672
references.citation: Regul Pept. 1985 May;11(1):35-41
references.pmid: 2861626