title: Glutamatergic antipsychotic drugs: a new dawn in the treatment of schizophrenia?
abstract: Growing evidence for glutamate abnormalities in schizophrenia support the development of novel antipsychotic agents targeting this system. Early studies investigating modulation of the glutamate system using glycine, D-serine and sarcosine in patients with schizophrenia have demonstrated significant effects, particularly on negative symptoms, conventionally thought to be refractory to antipsychotic drug treatment. Drugs targeting the glutamate system also have a completely different side-effect profile to dopamine D2 antagonists, with no propensity to extrapyramidal side effects, prolactinaemia or weight gain. It has been hypothesized that glutamatergic drugs may be of benefit to the 20-30% of individuals with schizophrenia who fail to show any response to dopaminergic agents, and may be particularly useful in the early stages of the illness, where they may be disease-modifying. A number of glutamatergic compounds have been reported as having promising results in phase II drug trials. If these reach the clinic, they will represent the first truly novel approach to pharmacotherapy in schizophrenia for more than 50 years.
authors: James M
authors: JM
authors: Stone
keywords: antipsychotic drugs; glutamate; pharmacology; psychosis; schizophrenia
references: Nat Med. 2007 Sep;13(9):1102-7
references: 17767166
references: Schizophr Res. 2009 Mar;108(1-3):69-77
references: 19097753
references: J Pharmacol Exp Ther. 2009 Dec;331(3):1126-36
references: 19755662
references: Biol Psychiatry. 2007 Oct 1;62(7):739-46
references: 17511968
references: Biochem Soc Trans. 2004 Nov;32(Pt 5):881-7
references: 15494040
references: Am J Psychiatry. 1998 Jun;155(6):751-60
references: 9619146
references: Arch Gen Psychiatry. 2008 Feb;65(2):154-64
references: 18250253
references: Arch Gen Psychiatry. 1999 Sep;56(9):781-7
references: 12884883
references: Arch Gen Psychiatry. 1997 Oct;54(10):959-65
references: 9337777
references: Braz J Med Biol Res. 2006 Apr;39(4):421-9
references: 16612464
references: Mol Psychiatry. 2006 Feb;11(2):118-9
references: 16189506
references: Brain Res. 2007 Jun 18;1154:154-62
references: 17488642
references: Int Rev Neurobiol. 2007;78:69-108
references: 17349858
references: Psychopharmacology (Berl). 2005 Apr;179(1):4-29
references: 15731895
references: Life Sci. 2008 Aug 1;83(5-6):170-5
references: 18590745
references: J Clin Exp Neuropsychol. 2006 Feb;28(2):270-82
references: 16484098
references: Cell Mol Neurobiol. 2006 Jul-Aug;26(4-6):365-84
references: 16773445
references: Biol Psychiatry. 2010 Oct 1;68(7):599-602
references: 20638047
references: J Pharmacol Exp Ther. 2005 Apr;313(1):199-206
references: 15608073
references: Int Clin Psychopharmacol. 1998 Mar;13 Suppl 3:S21-6
references: 9690966
references: Schizophr Res. 2009 Apr;109(1-3):10-4
references: 19186030
references: Psychopharmacology (Berl). 2004 Jun;174(1):39-44
references: 15205877
references: J Neurochem. 2004 Dec;91(5):1219-30
references: 15569265
references: Pharmacol Rev. 1999 Mar;51(1):7-61
references: 10049997
references: J Physiol. 2004 Jun 1;557(Pt 2):489-500
references: 15064326
references: J Clin Psychiatry. 2010 Feb;71(2):138-49
references: 19895780
references: Arch Gen Psychiatry. 1995 Dec;52(12):998-1007
references: 7492260
references: Eur J Pharmacol. 2005 Apr 11;512(2-3):199-205
references: 15840405
references: Eur Psychiatry. 2002 Nov;17(7):371-8
references: 12547302
references: Biol Psychiatry. 2009 Sep 15;66(6):533-9
references: 19559402
references: Am J Psychiatry. 2002 Nov;159(11):1944-6
references: 12411236
references: Neuropsychopharmacology. 2006 Jul;31(7):1356-61
references: 16319915
references: J Med Chem. 2004 Nov 18;47(24):5825-8
references: 15537338
references: Neuropsychopharmacology. 2007 Sep;32(9):2004-10
references: 17228338
references: Neuroreport. 2001 Sep 17;12(13):2971-4
references: 11588613
references: Schizophr Res. 2009 Sep;113(2-3):189-99
references: 19628375
references: J Psychopharmacol. 2010 Nov;24(11):1681-7
references: 19648218
references: Neuropsychopharmacology. 2006 Apr;31(4):795-803
references: 16052245
references: Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):336-9
references: 17884273
references: Br J Psychiatry. 2010 Oct;197(4):285-90
references: 20884951
references: Psychiatry Res. 2009 Apr 30;172(1):44-8
references: 19239984
references: Am J Psychiatry. 2006 Apr;163(4):600-10
references: 16585434
references: Synapse. 2009 Oct;63(10):935-9
references: 19588471
references: Pharmacol Biochem Behav. 2010 Apr;95(2):223-9
references: 20122952
references: Science. 1975 Jun 20;188(4194):1217-9
references: 1145194
references: Mol Vis. 2008;14:2190-203
references: 19052649
references: J Med Chem. 2010 Jun 24;53(12):4603-14
references: 20491477
references: Mol Psychiatry. 2010 Mar;15(3):308-18
references: 18645571
references: Eur J Pharmacol. 2002 Aug 2;449(1-2):121-5
references: 12163115
references: Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jan 15;35(1):198-202
references: 21062637
references: Neuropsychopharmacology. 2009 May;34(6):1514-22
references: 19052539
references: J Psychopharmacol. 2007 Jun;21(4):440-52
references: 17259207
references: Neuropharmacology. 2010 Mar;58(3):632-9
references: 19951716
references: Am J Psychiatry. 2008 Dec;165(12):1585-93
references: 18923067
references: Psychiatry Res. 2000 May 15;98(3):163-75
references: 10821999
references: Schizophr Res. 2005 Mar 1;73(2-3):153-7
references: 15653258
references: J Neurosci. 1997 Apr 15;17(8):2921-7
references: 9092613
references: Neuropsychopharmacology. 2010 Feb;35(3):764-74
references: 19924114
references: Annu Rev Physiol. 2003;65:401-27
references: 12524459
references: Eur J Pharmacol. 2010 Aug 10;639(1-3):26-32
references: 20371234
references: Psychopharmacology (Berl). 2006 Nov;188(4):408-24
references: 17006715
references: Aust N Z J Psychiatry. 2000 Nov;34 Suppl:S164-9
references: 11129303
references: Biol Psychiatry. 2008 Jan 1;63(1):9-12
references: 17659263
references: Neuropharmacology. 2008 Oct;55(5):743-54
references: 18602930
references: Curr Psychiatry Rep. 2001 Oct;3(5):413-7
references: 11559479
references: Schizophr Res. 2004 Nov 1;71(1):103-12
references: 15374578
references: Neuropsychopharmacology. 2003 Sep;28(9):1622-32
references: 12825094
references: J Neurochem. 2007 Jun;101(6):1471-82
references: 17286592
references: Am J Psychiatry. 2004 Jun;161(6):975-84
references: 15169685
references: J Psychiatr Res. 1999 Nov-Dec;33(6):523-33
references: 10628529
references: Neurosci Lett. 2006 May 15;399(1-2):91-5
references: 16490313
references: Neuron Glia Biol. 2004 Aug;1(3):297-305
references: 18634603
references: J Clin Psychiatry. 2005 Aug;66(8):1012-5
references: 16086616
references: Curr Pharm Des. 2010;16(5):522-37
references: 19909229
references: Mol Psychiatry. 2004 Nov;9(11):984-97, 979
references: 15278097
references: Arch Gen Psychiatry. 2009 Jan;66(1):95-105
references: 19124693
references: Neuropharmacology. 2004 Dec;47(8):1135-45
references: 15567423
references: Eur J Pharmacol. 1974 Sep;28(1):172-7
references: 4609777
references: Mol Psychiatry. 2005 Jan;10(1):40-68; image 5
references: 15263907
references: J Physiol. 2007 Jan 1;578(Pt 1):233-47
references: 17053036
references: Am J Psychiatry. 2003 Dec;160(12):2231-3
references: 14638596
references: Trends Neurosci. 2001 Jun;24(6):330-4
references: 11356504
references: Neuroscience. 2003;117(3):697-706
references: 12617973
references: Arch Gen Psychiatry. 1994 Mar;51(3):199-214
references: 8122957
references: Prog Neuropsychopharmacol Biol Psychiatry. 2003 Oct;27(7):1081-90
references: 14642968
references: Nat Rev Neurosci. 2005 Apr;6(4):312-24
references: 15803162
references: Neuropharmacology. 2009 Oct-Nov;57(5-6):531-8
references: 19627999
references: Br J Psychiatry. 2008 Apr;192(4):306-7
references: 18378995
references: Am J Psychiatry. 2004 Jun;161(6):1116-8
references: 15169703
references: Eur J Pharmacol. 2010 Aug 10;639(1-3):91-8
references: 20371226
references: J Psychopharmacol. 2010 Jul;24(7):953-64
references: 19939865
references: Arch Gen Psychiatry. 2005 Sep;62(9):985-94
references: 16143730
references: Synapse. 2009 Mar;63(3):247-51
references: 19084908
references: Schizophr Res. 1991 Sep;5(2):123-34
references: 1931805
references: Arch Gen Psychiatry. 1988 Sep;45(9):789-96
references: 3046553
references: Curr Pharm Des. 2009;15(22):2594-602
references: 19689330
references: Psychopharmacology (Berl). 2008 Apr;197(3):401-8
references: 18176855
references: Epilepsia. 2000;41(S1):10-6
references: 10768293
references: Neurosci Lett. 2000 Aug 4;289(2):147-51
references: 10904141