REVIEW PAPER
The NMDA receptor ligands in anti-depressant therapy
1
Katedra i Zakład Fizjologii Człowieka, Uniwersytet Medyczny w Lublinie
2
Katedra i Zakład Farmacji Stosowanej, Uniwersytet Medyczny w Lublinie
Corresponding author
Weronika Stasiuk
Katedra i Zakład Fizjologii Człowieka, Uniwersytet Medyczny w Lublinie, ul. Radziwiłłowska 11, 20-080 Lublin
Katedra i Zakład Fizjologii Człowieka, Uniwersytet Medyczny w Lublinie, ul. Radziwiłłowska 11, 20-080 Lublin
Med Og Nauk Zdr. 2016;22(3):176-180
KEYWORDS
ABSTRACT
Introduction:
A new direction in research on depressive disorders focuses on reducing the activity of the NMDA receptor, which opens up new possibilities for the treatment of diseases caused by the excessive activity of the glutamatergic system.
Objective:
The aim of this work is the study of ligands (especially antagonists) of the NMDA receptor, which influence its expression and function as well as their impact on the action of classic anti-depressant medications.
Description of the state of knowledge:
The effectiveness of currently utilized depressive disorder treatment methods is unsatisfactory and linked to many side effects. It is also a worrying fact that many patients develop drug resistance. This is why there is a continued effort for the development of newer, more effective treatment methods. It has been shown that one of the key anti-depressant mechanisms of action is through the blockage of the NMDA receptor.
Conclusions:
The introduction into the treatment regime of antagonists of the NMDA receptor opens new therapeutic possibilities in the treatment of depressive disorders, as well as being a potential alternative in the treatment of drug resistant forms of the disease.
A new direction in research on depressive disorders focuses on reducing the activity of the NMDA receptor, which opens up new possibilities for the treatment of diseases caused by the excessive activity of the glutamatergic system.
Objective:
The aim of this work is the study of ligands (especially antagonists) of the NMDA receptor, which influence its expression and function as well as their impact on the action of classic anti-depressant medications.
Description of the state of knowledge:
The effectiveness of currently utilized depressive disorder treatment methods is unsatisfactory and linked to many side effects. It is also a worrying fact that many patients develop drug resistance. This is why there is a continued effort for the development of newer, more effective treatment methods. It has been shown that one of the key anti-depressant mechanisms of action is through the blockage of the NMDA receptor.
Conclusions:
The introduction into the treatment regime of antagonists of the NMDA receptor opens new therapeutic possibilities in the treatment of depressive disorders, as well as being a potential alternative in the treatment of drug resistant forms of the disease.
REFERENCES (50)
1.
Renaud J, Bedard E. Depression in the elderly with visual impairment and its association with quality of life. Clin Interv Aging. 2013; 8: 931–943.
2.
Hashimoto K. The role of glutamate on the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35: 1558–1568.
3.
Pilc A, Wieronska JM, Skolnick P. Glutamate-based antidepressants: preclinical psychopharmacology. Biol Psychiatry. 2013; 73: 1125–32.
4.
Duman RS. Aghajanian GK. Synaptic dysfunction in depression: Potential therapeutic target. Science. 2012; 338: 68–72.
5.
Gupta D, Radhakrishnan M, Bhatt S, Kurhe Y. Role of hypothalamic-pituitary-adrenal-axis in affective disorders: anti-depressant and anxiolytic activity of partial 5-HT1A agonist in adrenalectomised rats. Indian J Psychol Med. 2013; 35: 290–298.
6.
Hashimoto K. BDNF and proBDNF as biomarkers for bipolar disorder. Bri J Psychiatry. 2014; 205: 410.
7.
Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, Kammerer WA, Quezado Z, Luckenbaugh DA, Salvadore G, Machado-Vieira R, Manji HK, Zarate CAJr. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry. 2010; 67: 793–802.
8.
Permoda-Osip A, Rybakowski J. Glutamatergic Conception of Mood Disorders. Psychiatr Pol. 2011; 45: 875–888.
9.
Saveanu R, Etkin A, Duchemin AM, et al. The International Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment. J Psychiatr Res. 2015; 61: 1–12.
10.
Sokół-Szawłowska M. Objawy niepożądane po lekach przeciwdepresyjnych. Side effects of antidepressants. Terapia. 2011; 19 (1): 37–42.
11.
Mauskopf JA, Simon GE, Kalsekar A, et al. Nonresponse, partial response, and failure to achieve remission: humanistic and cost burden in major depressive disorder. Depress Anxiety. 2009; 26: 83–97.
12.
Levinstein MR,Samuels BA. Mechanisms underlying the antidepressant response and treatment resistance. Front Behav Neurosci. 2014; 8: 208.
13.
Łoza B, Czernikiewicz A, Patejuk-Mazurek I. Politerapia zaburzeń depresyjnych. Preferencje polskich psychiatrów. Psychiatria. 2007; 4: 97–104.
14.
Glasgow NG, Siegler RB, Johnson JW. Molecular bases of NMDA receptor subtype-dependent properties. J Physiol. 2015; 593: 83–95.
15.
Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev. 2010; 62: 405–496.
16.
Chaffey H, Chazot PL. NMDA receptor subtypes: structure, function and therapeutics. Curr Anaesth Crit Care. 2008; 19: 183–201.
17.
Zhou X, Chen Z, Yun W, et al. Extrasynaptic NMDA receptor in excitotoxicity: function revisited. Neuroscientist. 2015; 21: 337–344.
18.
Crews L, Masliah E. Molecular mechanisms of neurodegeneration in Alzheimer›s disease. Hum Mol Genet. 2010; 19: 12–20.
19.
Martucci L, Wong AH, De LV, Likhodi O, Wong GW, King N, Kennedy JL. N-methyl-D-aspartate receptor NR2B subunit gene GRIN2B in schizophrenia and bipolar disorder: Polymorphisms and mRNA Levels. Schizophr Res. 2006; 84: 214–221.
20.
Phelps LE, Brutsche N, Moral JR, Luckenbaugh DA, Manji HK, Zarate CA Jr. Family history of alcohol dependence and initial antidepressant response to an N-methyl-D-aspartate antagonist. Biol Psychiatry. 2009; 65: 181–184.
21.
Yurkewicz L, Weaver J, Bullock MR, Marshall LF. The effect of the selective NMDA receptor antagonist traxoprodil in the treatment of traumatic brain injury. J Neurotrauma. 2005; 22: 1428–1443.
22.
Ghasemi M, Philips C, Trillo L, De Miguel Z, Das D, Salehi A. The role of NMDA receptors in the pathophysiology and treatment of mood disorders. Neurosci Biobehav Rev. 2014; 47: 336–58.
23.
Tokita K, Yamaji T, Hashimoto K. Roles of glutamate signaling in prec¬linical and/or mechanistic models of depression. Pharmacol Biochem Behav. 2012; 100: 688–704.
24.
Williams NR, Schatzberg AF. NMDA antagonist treatment of depression. Curr Pin Neurobiol. 2016; 36: 112–7.
25.
Steciuk M, Kram M, Kramer GL et al. immobilization-induced gluta¬mate efflux in medial prefrontal cortex: blockade by Mk-801, a selective NMDA receptor antagonist. Stress. 2000; 3: 195–199.
26.
Papp M, Moryl E. Similar effect of chronic treatment with imipramine and the NMDA antagonists CGP 37849 and MK-801 in a chronic mild stress model of depression in rats. Eur J Neuropsychopharmacol. 1993; 3: 348–349.
27.
Klimek V, Papp M. The effect of MK-801 and imipramine on beta-adrenergic and 5-HT2 receptors in the chronic 18. mild stress model of depression in rats. Pol J Pharmacol. 1994; 46: 67–69.
28.
Poleszak E, Wlaź P, Wróbel A, Dybała M, Sowa M, Fidecka S, Pilc A, Nowak G. Activation of the NMDA/glutamate receptor complex anta-gonizes the NMDA antagonist-induced antidepressant-like effects in the forced swim test. Pharmacol Rep. 2007; 59: 595–600.
29.
Wlaź P, Kasperek R, Wlaź A, Szumilo M, Wróbel A, Nowak G, Poleszak E. NMDA and AMPA receptors are involved in the antidepressant-like activity of tianeptine in the forced swim test in mice. Pharmacol Rep. 2011; 63: 1526–1532.
30.
Heresco-Levy U, Gelfin G, Bloch B, Levin R, Edelman S, Javitt DC, Kremer I. A randomized add-on trial of high-dose D-cycloserine for treatment-resistant depression. Int. J Neuropsychopharmacol. 2013; 16: 501–506.
31.
Moskal JR, Burch R, Burgdorf JS et al. GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produ¬ces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists. Expert Opin Investig Drugs. 2014; 23: 243–254.
32.
Dybała M, Siwek A, Poleszak E, Pilc A, Nowak G. Lack of NMDA-AMPA interaction in antidepressant-like effect of CGP 37849, an antagonist of NMDA receptor, in the forced swim test. J Neural Transm (Vienna). 2008; 115: 1519–20.
33.
Poleszak E, Wośko S, Serefko A, Szopa A, Wlaź A, Szewczyk B, Nowak G, Wlaź P. Effects of ifenprodil on the antidepressant-like activity of NMDA ligands in the forced swim test in mice. Prog Neuropsychop harmacol Biol Psychiatry. 2013; 46: 29–35.
34.
Poleszak E, Wośko S, Serefko A, Wlaź A, Kasperek R, Dudka J, Wróbel A, Nowak G, Wlaź P. The effects of ifenprodil on the activity of antidepressant drugs in the forced swim test in mice. Pharmacol Rep. 2014; 66: 1031–1036.
35.
Poleszak E, Stasiuk W, Szopa A, Wyska E, Serefko A, Oniszczuk A, Wośko S, Świąder K, Wlaź P. Traxoprodil, a selective antagonist of the NR2B subunit of the NMDA receptor, potentiates the antidepressant-like ef¬fects of certain antidepressant drugs in the forced swim test in mice. Me¬tab Brain Dis. 2016; http://www.ncbi.nlm.nih.gov/pu....
36.
Nutt JG, Gunzler SA, Kirchhoff T, Hogarth P, Weaver JL, Krams M, Jamerson B, Menniti FS, Landen JW. Effects of a NR2B selective NMDA glutamate antagonist, CP-101,606, on dyskinesia and parkinsonism. Mov Disord. 2008; 23: 1860–1866.
37.
Preskorn SH, Baker B, Kolluri S, Menniti FS, Krams M, Landen JW. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. J Clin Psychopharmacol. 2008; 28: 631–637.
38.
Pochwat B, Szewczyk B, Sowa-Kućma M et al. Antidepressant-like activity of magnesium in the chronic mild stress model in rats: altera-tions in the NMDA receptor subunits. Int J Neuropsychopharmacol. 2014; 17: 393–405.
39.
Swardfager W, Herrmann N, Mcintyre RS, Mazereeuw G, Goldberger K, Cha DS et al. Potential roles of zink in the pathophysiology and treatment of major depressive disorder. Neurosci Biobehav Rev. 2013; 37: 911–29.
40.
Cunha MP, Machado DG, Bettio LEB, Capra JC, Rodrigues ALS. Interaction of zinc with antidepressants in the tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32: 1913–1920.
41.
Szewczyk B, Poleszak E, Wlaź P, Wróbel A, Blicharska E, Cichy A, Dybała M, Siwek A, Pomierny-Chamioło L, Piotrowska A, Brański P, Pilc A, Nowak G. The involvement of serotonergic system in the antidepressant effect of zinc in the forced swim test. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33: 323–329.
42.
Siwek M, Dudek D, Paul IA, Sowa-Kućma M, Zięba A, Popik P, Pilc A, Nowak G. Zinc supplementation augments efficacy of imipramine in treatment resistant patients: a double blind, placebo-controlled study. J Affect Disord. 2009; 118: 187–195.
43.
Gosek P, Chojnacka M, Bieńkowski P, Święcicki L. Antidepressant effect of ketamine, a N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, in the therapy of treatment-resistant depression. Psychiatr Pol. 2012; 46: 283–294.
44.
Ballard ED, Ionescu DF, Vande Voort JL, et al. Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depres¬sion and anxiety. J Psychiatr Res. 2014; 58: 161–166.
45.
Sanacora G, Schatzberg AF. Ketamine: promising path or false prophecy in the development of novel therapeutics for mood disorders? Neuropsychopharmacology. 2015; 40: 259–267.
46.
Larkin GL, Beautrais AL. A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. Int J Neuropsychopharmacol. 2011; 14: 1127–1131.
47.
Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006; 63: 856–64.
48.
Sanacora G, Smith MA, Pathak S et al. Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychomimetic adverse effects. Mol Psychiatry. 2014; 19: 978–985.
49.
Rogóż Z, Skuza G, Daniel WA, Wójcikowski J, Dudek D, Wróbel A. Amantadine as an additive treatment in patients suffering from drug-resistant unipolar depression. Pharmacol Rep. 2007; 59: 778–784.
50.
Smith EG, Deligiannidis KM, Ulbricht CM, et al. Antidepressant augmentation using the N-methyl-D-aspartate antagonist memantine: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2013; 74: 966–973.
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