title: Newer antipsychotics and upcoming molecules for schizophrenia.
abstract: BACKGROUND
  The management of schizophrenia has seen significant strides over the last few decades, due to the increasing availability of a number of antipsychotics. Yet, the diminished efficacy in relation to the negative and cognitive symptoms of schizophrenia, and the disturbing adverse reactions associated with the current antipsychotics, reflect the need for better molecules targeting unexplored pathways.
  
  
  OBJECTIVE
  To review the salient features of the recently approved antipsychotics; namely, iloperidone, asenapine, lurasidone and blonanserin.
  
  
  METHODS
  We discuss the advantages, limitations and place in modern pharmacotherapy of each of these drugs. In addition, we briefly highlight the new targets that are being explored.
  
  
  RESULTS
  Promising strategies include modulation of the glutamatergic and GABAergic pathways, as well as cholinergic systems.
  
  
  CONCLUSIONS
  Although regulatory bodies have approved only a handful of antipsychotics in recent years, the wide spectrum of targets that are being explored could eventually bring out antipsychotics with improved efficacy and acceptability, as well as the potential to revolutionize psychiatric practice.
authors.affiliation: Department of Cardiology, SRM Medical College Hospital & Research Centre, Chennai, India. melvingeorge2003@gmail.com
authors.forename: Melvin
authors.initials: M
authors.lastname: George
authors.forename: Radhika
authors.initials: R
authors.lastname: Amrutheshwar
authors.forename: Ravi Philip
authors.initials: RP
authors.lastname: Rajkumar
authors.forename: Shivanand
authors.initials: S
authors.lastname: Kattimani
authors.forename: Steven Aibor
authors.initials: SA
authors.lastname: Dkhar
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003986:Dibenzocycloheptenes; D055808:Drug Discovery; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use; D006801:Humans; D054833:Isoindoles / Q000627:therapeutic use; D007555:Isoxazoles / Q000627:therapeutic use; D000069056:Lurasidone Hydrochloride; D010879:Piperazines / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D013844:Thiazoles / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D054833:Isoindoles; D007555:Isoxazoles; D010879:Piperazines; D010880:Piperidines; D013844:Thiazoles; C079310:blonanserin; C522667:asenapine; D000069056:Lurasidone Hydrochloride; C081732:iloperidone
references.citation: Ann Gen Psychiatry. 2010 Jun 24;9:27
references.pmid: 20573264
references.citation: Pharmacol Biochem Behav. 2010 Aug;96(2):175-80
references.pmid: 20460137
references.citation: Int J Clin Pract. 2011 Feb;65(2):189-210
references.pmid: 21129135
references.citation: Bioorg Med Chem Lett. 2001 Feb 12;11(3):319-21
references.pmid: 11212100
references.citation: Mol Psychiatry. 2009 Nov;14(11):1024-31
references.pmid: 18521091
references.citation: Psychopharmacology (Berl). 2012 May;221(1):115-31
references.pmid: 22068461
references.citation: Am J Psychiatry. 2008 Aug;165(8):1040-7
references.pmid: 18381905
references.citation: J Clin Psychopharmacol. 2011 Jun;31(3):349-55
references.pmid: 21508856
references.citation: Am J Psychiatry. 2008 Jun;165(6):774
references.pmid: 18519539
references.citation: Biochem Pharmacol. 2009 Oct 1;78(7):880-8
references.pmid: 19615981
references.citation: Pharmacol Res. 2012 Jul;66(1):60-5
references.pmid: 22465688
references.citation: Med Lett Drugs Ther. 2011 Feb 21;53(1358):13-4
references.pmid: 21372761
references.citation: J Psychopharmacol. 2009 Jan;23(1):65-73
references.pmid: 18308814
references.citation: Neuropharmacology. 2010 Feb;58(2):365-73
references.pmid: 19835892
references.citation: J Clin Psychiatry. 2009 Jun;70(6):829-36
references.pmid: 19497249
references.citation: Psychopharmacology (Berl). 2011 Dec;218(3):579-87
references.pmid: 21625907
references.citation: Schizophr Res. 1993 Aug;10(2):131-41
references.pmid: 8398945
references.citation: Clin Schizophr Relat Psychoses. 2011 Jan;4(4):251-7
references.pmid: 21177242
references.citation: Pharmacogenomics. 2008 Mar;9(3):289-301
references.pmid: 18303965
references.citation: Biol Psychiatry. 2011 Mar 1;69(5):442-9
references.pmid: 21145041
references.citation: Mol Psychiatry. 2009 Aug;14(8):804-19
references.pmid: 18521090
references.citation: Nat Med. 2007 Sep;13(9):1102-7
references.pmid: 17767166
references.citation: J Pharmacol Exp Ther. 2010 Apr;333(1):328-40
references.pmid: 20093397
references.citation: Schizophr Res. 2011 Oct;132(1):50-3
references.pmid: 21840177
references.citation: Ther Clin Risk Manag. 2011;7:239-50
references.pmid: 21753886
references.citation: Eur J Pharmacol. 2007 Oct 31;572(2-3):171-4
references.pmid: 17628535
references.citation: Am J Health Syst Pharm. 2011 Feb 15;68(4):301-8
references.pmid: 21289324
references.citation: J Clin Psychiatry. 2009 Oct;70(10):1416-23
references.pmid: 19906345
references.citation: J Clin Psychiatry. 2010 Feb;71(2):138-49
references.pmid: 19895780
references.citation: Psychiatry Clin Neurosci. 2011 Jun;65(4):389-91
references.pmid: 21569175
references.citation: Adv Ther. 2013 Feb;30(2):114-26
references.pmid: 23361833
references.citation: Int J Neuropsychopharmacol. 2010 Aug;13(7):891-903
references.pmid: 19835668
references.citation: Nature. 2011 Dec 06;480(7376):161-2
references.pmid: 22158218
references.citation: Curr Pharm Des. 2011;17(2):112-20
references.pmid: 21355838
references.citation: J Pharmacol Exp Ther. 2009 May;329(2):459-68
references.pmid: 19223665
references.citation: Schizophr Res. 2010 Aug;121(1-3):118-24
references.pmid: 20570110
references.citation: Am J Psychiatry. 2007 Aug;164(8):1269
references.pmid: 17671295
references.citation: Eur J Pharmacol. 2009 Mar 15;606(1-3):102-8
references.pmid: 19374836
references.citation: J Pharmacol Exp Ther. 2008 Dec;327(3):827-39
references.pmid: 18753411
references.citation: Schizophr Res. 2012 Apr;136(1-3):25-31
references.pmid: 22169248
references.citation: Pharmacol Biochem Behav. 2010 Mar;95(1):23-30
references.pmid: 19995568
references.citation: Expert Opin Pharmacother. 2010 Aug;11(12):2087-93
references.pmid: 20586713
references.citation: J Clin Psychopharmacol. 2008 Apr;28(2 Suppl 1):S29-35
references.pmid: 18334910
references.citation: Trends Pharmacol Sci. 2008 Feb;29(2):91-8
references.pmid: 18187211
references.citation: Expert Opin Investig Drugs. 2008 Jan;17(1):61-75
references.pmid: 18095919
references.citation: Hum Psychopharmacol. 2012 Jan;27(1):24-32
references.pmid: 22161738
references.citation: Postgrad Med. 2011 Mar;123(2):153-62
references.pmid: 21474903
references.citation: J Pharmacol Exp Ther. 2008 Jul;326(1):230-9
references.pmid: 18420599
references.citation: Expert Opin Investig Drugs. 2009 Nov;18(11):1715-26
references.pmid: 19780705
references.citation: Pharmacopsychiatry. 2011 Sep;44(6):195-235
references.pmid: 21969060
references.citation: Neuropsychopharmacology. 2012 Feb;37(3):660-8
references.pmid: 22048460
references.citation: Drugs Today (Barc). 2011 Nov;47(11):807-16
references.pmid: 22146224
references.citation: CNS Drugs. 2011 Feb;25(2):129-43
references.pmid: 21254789
references.citation: J Psychopharmacol. 2012 Sep;26(9):1265-70
references.pmid: 22182741
references.citation: Curr Pharm Biotechnol. 2012 Jun;13(8):1572-86
references.pmid: 22283753
references.citation: Eur J Clin Pharmacol. 2010 Sep;66(9):899-902
references.pmid: 20490472
references.citation: Expert Opin Pharmacother. 2010 Aug;11(12):2107-15
references.pmid: 20642375
references.citation: CNS Drugs. 2009 Sep;23(9):781-92
references.pmid: 19689168
references.citation: J Clin Psychopharmacol. 2010 Apr;30(2):106-15
references.pmid: 20520283
references.citation: Schizophr Res. 2010 Sep;122(1-3):1-23
references.pmid: 20655178
references.citation: CNS Drugs. 2009;23(7):615-25
references.pmid: 19552488
references.citation: Neuropsychiatr Dis Treat. 2011;7:325-39
references.pmid: 21655346
references.citation: J Clin Psychiatry. 2009 Jun;70(6):801-9
references.pmid: 19573479
references.citation: J Clin Psychopharmacol. 2008 Apr;28(2 Suppl 1):S20-8
references.pmid: 18334909
references.citation: J Clin Psychopharmacol. 2008 Apr;28(2 Suppl 1):S4-11
references.pmid: 18334911
references.citation: Bioorg Med Chem Lett. 2012 Jan 1;22(1):235-9
references.pmid: 22142545
references.citation: Nature. 2009 Aug 6;460(7256):748-52
references.pmid: 19571811
references.citation: Schizophr Res. 2011 Apr;127(1-3):188-94
references.pmid: 21277745
references.citation: J Pharmacol Exp Ther. 2010 Jul;334(1):171-81
references.pmid: 20404009
references.citation: Psychopharmacology (Berl). 2012 Apr;220(3):591-8
references.pmid: 21947320
references.citation: Schizophr Res. 2011 Nov;132(2-3):101-7
references.pmid: 21889878
references.citation: Hum Psychopharmacol. 2012 Jan;27(1):90-100
references.pmid: 22278973
references.citation: Clin Neuropharmacol. 2010 Jul;33(4):169-75
references.pmid: 20661022
references.citation: CNS Drugs. 2010 Jan;24(1):65-84
references.pmid: 20030420
references.citation: Neuropsychopharmacology. 2007 Jun;32(6):1272-83
references.pmid: 17119538
references.citation: Hum Psychopharmacol. 2013 Mar;28(2):134-41
references.pmid: 23417765
references.citation: Psychopharmacology (Berl). 2009 Jan;201(4):483-94
references.pmid: 18762914
references.citation: J Clin Psychopharmacol. 2013 Apr;33(2):162-9
references.pmid: 23422369
references.citation: Neuropsychopharmacology. 2009 Apr;34(5):1322-9
references.pmid: 19005465
references.citation: Int Clin Psychopharmacol. 2012 May;27(3):165-76
references.pmid: 22395527
references.citation: P T. 2011 Aug;36(8):489-92
references.pmid: 21935296
references.citation: Psychopharmacology (Berl). 2013 Jan;225(2):329-39
references.pmid: 22868411
references.citation: Biol Psychiatry. 2011 Jan 1;69(1):12-8
references.pmid: 20965497
references.citation: Cell Mol Neurobiol. 2007 Aug;27(5):609-39
references.pmid: 17554626
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2002 Apr;26(3):553-60
references.pmid: 11999907
references.citation: Schizophr Res. 2012 Jun;138(1):35-8
references.pmid: 22483162
references.citation: Neuropharmacology. 2012 Mar;62(3):1371-80
references.pmid: 21420988
references.citation: Neuropsychiatr Dis Treat. 2009;5:483-90
references.pmid: 19851515
references.citation: J Clin Psychopharmacol. 2008 Apr;28(2 Suppl 1):S12-9
references.pmid: 18334908
references.citation: Schizophr Bull. 2004;30(2):255-64
references.pmid: 15279044