title: Treating schizophrenia symptoms with an alpha7 nicotinic agonist, from mice to men.
abstract: Current antipsychotic treatments fail to fully address the range of symptoms of schizophrenia, particularly with respect to social and occupational dysfunctions. Recent work has highlighted the role of nicotinie in both cognitive and attentional deficits as well as deficient processing of repetitive sensory information. The predilection for schizophrenia patients to be extremely heavy cigarette smokers may be related to their attempt to compensate for a reduction in hippocampal alpha7 nicotinic cholinergic receptors by delivering exogenous ligand to the remaining receptors. Studies in rodent models of both learning and memory deficits and deficits in sensory inhibition have confirmed a role for the alpha7 subtype of the nicotinic cholinergic receptor in these processes. Rodent studies also demonstrated the efficacy of a selective partial alpha7 nicotinic agonist, DMXBA, to improve these deficits. Subsequent human clinical trials demonstrated improved sensory inhibition in 12 schizophrenia patients and showed improvement in several subtests of the RBANS learning and memory assessment instrument. These data suggest that therapeutic agents selected for alpha7 nicotinic activity may have utility in treating certain symptoms of schizophrenia.
authors: Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA. ann.olincy@uchsc.edu
authors: Ann
authors: A
authors: Olincy
authors: Karen E
authors: KE
authors: Stevens
mesh_terms: D000818:Animals; D001597:Benzylidene Compounds / Q000627:therapeutic use*; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D006801:Humans; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D001597:Benzylidene Compounds; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C088936:3-(2,4-dimethoxybenzylidene)anabaseine
references: Arch Gen Psychiatry. 2002 Dec;59(12):1085-96
references: 12470124
references: Psychopharmacology (Berl). 2001 Jul;156(2-3):284-90
references: 11549230
references: Biol Psychiatry. 1997 Jul 1;42(1):1-5
references: 9193735
references: Biol Psychiatry. 1997 May 15;41(10):1035-44
references: 9129784
references: Neuropsychol Rev. 1996 Jun;6(2):61-79
references: 8976498
references: Pharmacol Biochem Behav. 1997 May-Jun;57(1-2):231-41
references: 9164577
references: Neurosci Lett. 1995 May 5;190(2):133-6
references: 7644122
references: Arch Gen Psychiatry. 2005 Jun;62(6):649-59
references: 15939842
references: J Pharmacol Exp Ther. 1998 Dec;287(3):918-25
references: 9864273
references: Psychopharmacology (Berl). 2003 Sep;169(3-4):332-9
references: 12759805
references: J Physiol Paris. 1998 Jun-Aug;92(3-4):309-16
references: 9789829
references: Harv Rev Psychiatry. 1994 Nov-Dec;2(4):179-92
references: 9384901
references: Psychiatry Res. 1991 Dec;39(3):257-68
references: 1798824
references: Neuropsychopharmacology. 2008 Feb;33(3):480-90
references: 17443126
references: Psychopharmacology (Berl). 2006 Jul;187(1):47-55
references: 16767415
references: Am J Psychiatry. 1993 Dec;150(12):1856-61
references: 8238642
references: Behav Brain Res. 2000 Dec 20;117(1-2):197-208
references: 11099773
references: Biol Psychiatry. 1985 Dec;20(12):1284-96
references: 4063418
references: Psychopharmacology (Berl). 2001 Jul;156(2-3):234-58
references: 11549226
references: Exp Aging Res. 2000 Oct-Dec;26(4):323-36
references: 11091939
references: Br J Psychiatry. 1984 Oct;145:429-32
references: 6487916
references: Psychiatry Res. 1996 Sep 27;64(2):121-35
references: 8912954
references: Am J Med Genet. 1998 Sep 7;81(5):361-3
references: 9754620
references: J Biol Chem. 2007 May 4;282(18):13220-7
references: 17360707
references: Schizophr Res. 1993 Aug;10(2):131-41
references: 8398945
references: Psychopharmacology (Berl). 1998 Aug;138(3-4):217-30
references: 9725745
references: J Med Chem. 2006 Jul 13;49(14):4425-36
references: 16821801
references: Neuroreport. 1999 Jun 3;10(8):1779-82
references: 10501574
references: Behav Brain Res. 2000 Aug;113(1-2):97-103
references: 10942036
references: Am J Psychiatry. 1999 Dec;156(12):1944-50
references: 10588409
references: Clin Neurophysiol. 2004 Feb;115(2):396-401
references: 14744582
references: Neuropsychopharmacology. 2004 Jul;29(7):1378-85
references: 15138435
references: Am J Med Genet. 2001 Dec 8;105(8):662-8
references: 11803512
references: Arch Gen Psychiatry. 1984 Jun;41(6):607-12
references: 6732421
references: Neuropsychopharmacology. 2003 Mar;28(3):542-51
references: 12629535
references: Addict Behav. 1998 Mar-Apr;23(2):263-6
references: 9573430
references: Psychopharmacology (Berl). 2001 Mar 1;154(2):126-30
references: 11314674
references: Am J Med Genet. 2001 Dec 8;105(8):658-61
references: 11803511
references: Psychopharmacology (Berl). 1988;95(2):171-5
references: 3137593
references: Neurosci Lett. 2005 Apr 22;378(3):140-4
references: 15781147
references: Clin Electroencephalogr. 1991 Jan;22(1):40-5
references: 1991411
references: Am J Psychiatry. 1992 Sep;149(9):1189-94
references: 1503131
references: Biol Psychiatry. 1998 Jul 15;44(2):98-106
references: 9646891
references: Behav Brain Res. 2003 Dec 17;147(1-2):1-8
references: 14659564
references: Neuropsychopharmacology. 1999 Aug;21(2):195-202
references: 10432467
references: J Subst Abuse. 1989;1(4):407-16
references: 2485288
references: Schizophr Res. 1998 Sep 7;33(1-2):113-8
references: 9783351
references: Neuropharmacology. 1995 Jun;34(6):583-90
references: 7566493
references: Psychopharmacology (Berl). 1998 Apr;136(4):320-7
references: 9600576
references: Ciba Found Symp. 1990;152:169-80; discussion 180-5
references: 2209253
references: J Clin Psychiatry. 2006;67 Suppl 9:9-13; discussion 36-42
references: 16965183
references: Am J Psychiatry. 1995 Mar;152(3):453-5
references: 7864277
references: Pharmacol Biochem Behav. 1995 Jun-Jul;51(2-3):509-14
references: 7667377
references: Brain Res. 1992 Jul 31;587(1):130-6
references: 1525643
references: Neuropsychopharmacology. 2002 Dec;27(6):1056-70
references: 12464463
references: Bioorg Med Chem Lett. 2001 Feb 12;11(3):319-21
references: 11212100
references: Neuropsychopharmacology. 2007 Jan;32(1):17-34
references: 16936709
references: Biol Psychiatry. 2002 Oct 1;52(7):721-8
references: 12372663
references: Arch Gen Psychiatry. 1994 Feb;51(2):139-54
references: 8297213
references: Biol Psychiatry. 1999 Nov 15;46(10):1443-50
references: 10578459
references: Neuropsychobiology. 1999;39(1):10-7
references: 9892854
references: Schizophr Res. 1996 Nov 15;22(2):133-41
references: 8958597
references: J Chem Neuroanat. 2001 Jul;22(1-2):115-26
references: 11470559
references: Am J Med Genet. 2000 Apr 3;96(2):196-201
references: 10893497
references: Jpn J Pharmacol. 1998 Jan;76(1):23-9
references: 9517401
references: Arch Gen Psychiatry. 2006 Jun;63(6):630-8
references: 16754836
references: Ann N Y Acad Sci. 1992 Jul 1;658:111-27
references: 1497255
references: Neuropharmacology. 2003 Jun;44(8):1054-67
references: 12763099
references: Psychiatr Clin North Am. 2005 Sep;28(3):613-33, 626
references: 16122570
references: Brain Res. 1991 Apr 26;547(1):167-70
references: 1860068
references: Psychopharmacology (Berl). 2003 Feb;165(4):386-96
references: 12459928
references: Schizophr Res. 2005 Jul 1;76(1):67-72
references: 15927799
references: Am J Psychiatry. 1993 Apr;150(4):546-53
references: 8465868
references: Toxicon. 1971 Jan;9(1):15-22
references: 5539371
references: Am J Med Genet. 1999 Apr 16;88(2):109-12
references: 10206225
references: Eur J Pharmacol. 2000 Mar 30;393(1-3):179-95
references: 10771012
references: J Neurosci. 1998 Feb 15;18(4):1187-95
references: 9454829
references: Biol Psychiatry. 1999 Jul 1;46(1):125-9
references: 10394482
references: Psychopharmacology (Berl). 2002 Jan;159(3):248-57
references: 11862357
references: Biol Psychiatry. 2001 Oct 1;50(7):493-500
references: 11600102
references: Eur Neuropsychopharmacol. 1999 Jun;9(4):323-7
references: 10422893
references: Schizophr Res. 2006 Oct;87(1-3):307-15
references: 16854565
references: Mol Psychiatry. 2004 Mar;9(3):320-2
references: 14569275
references: Am J Psychiatry. 1999 Nov;156(11):1751-7
references: 10553739
references: J Med Chem. 2000 Nov 2;43(22):4045-50
references: 11063601
references: Brain Res. 1995 Mar 20;674(2):252-9
references: 7796104
references: J Neurochem. 1999 Oct;73(4):1590-7
references: 10501205
references: Neuropsychopharmacology. 1996 Nov;15(5):429-36
references: 8914115
references: Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):587-92
references: 9012828
references: Am J Psychiatry. 1992 Apr;149(4):488-93
references: 1554034
references: Curr Opin Psychiatry. 2007 May;20(3):268-72
references: 17415081
references: Psychopharmacology (Berl). 1999 Apr;143(2):158-65
references: 10326778
references: Pharmacol Biochem Behav. 1997 Aug;57(4):869-74
references: 9259018
references: JAMA. 2000 Nov 22-29;284(20):2606-10
references: 11086367
references: Brain Res. 1994 May 9;645(1-2):309-17
references: 8062092
references: Br J Pharmacol. 2004 Jul;142(5):843-50
references: 15197106
references: Am J Psychiatry. 1998 Dec;155(12):1691-4
references: 9842777
references: Eur J Pharmacol. 2000 Mar 30;393(1-3):141-6
references: 10771007
references: Biol Psychiatry. 1990 Sep 15;28(6):502-8
references: 1977478
references: Brain Res. 1997 Sep 12;768(1-2):49-56
references: 9369300
references: J Neurosci. 1993 May;13(5):1965-75
references: 8478687
references: Neuropsychopharmacology. 2002 May;26(5):583-94
references: 11927183
references: Acta Physiol Scand. 1990 Mar;138(3):427-8
references: 2327269
references: Biol Psychiatry. 1992 Oct 1;32(7):607-16
references: 1450287
references: Neuropsychopharmacology. 1996 Aug;15(2):152-62
references: 8840351
references: Pharmacol Toxicol. 1995 Mar;76(3):157-62
references: 7617539
references: J Pharmacol Exp Ther. 1997 Dec;283(3):979-92
references: 9399967
references: Hum Psychopharmacol. 2001 Jun;16(4):321-326
references: 12404567
references: Behav Brain Res. 2003 Aug 14;143(2):159-67
references: 12900042
references: Biol Psychiatry. 1995 Jul 1;38(1):22-33
references: 7548469
references: Neuropsychopharmacology. 2002 Sep;27(3):479-97
references: 12225705
references: Mol Pharmacol. 1995 Jan;47(1):164-71
references: 7838125
references: Psychopharmacology (Berl). 1992;108(4):485-94
references: 1410164
references: Neuropsychopharmacology. 2004 May;29(5):891-900
references: 14970827
references: Neuropsychopharmacology. 2002 Jan;26(1):75-85
references: 11751034
references: Am J Psychiatry. 2005 Feb;162(2):386-8
references: 15677607
references: Am J Psychiatry. 1986 Aug;143(8):993-7
references: 3487983
references: Schizophr Bull. 2000;26(1):119-36
references: 10755673
references: Biol Psychiatry. 2004 Apr 15;55(8):850-8
references: 15050867
references: Am J Med Genet. 1998 Jul 10;81(4):308-12
references: 9674976
references: Psychopharmacology (Berl). 2004 Jul;174(3):334-40
references: 14997272
references: Am J Med Genet. 1999 Apr 16;88(2):188-99
references: 10206241
references: Am J Med Genet. 2001 Dec 8;105(8):669-74
references: 11803513