Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia.
D1 partial agonism
D1 receptor
cognition
schizophrenia
Journal
Schizophrenia bulletin
ISSN: 1745-1701
Titre abrégé: Schizophr Bull
Pays: United States
ID NLM: 0236760
Informations de publication
Date de publication:
21 01 2022
21 01 2022
Historique:
pubmed:
24
8
2021
medline:
3
3
2022
entrez:
23
8
2021
Statut:
ppublish
Résumé
Decades of research have highlighted the importance of optimal stimulation of cortical dopaminergic receptors, particularly the D1R receptor (D1R), for prefrontal-mediated cognition. This mechanism is particularly relevant to the cognitive deficits in schizophrenia, given the abnormalities in cortical dopamine (DA) neurotransmission and in the expression of D1R. Despite the critical need for D1R-based therapeutics, many factors have complicated their development and prevented this important therapeutic target from being adequately interrogated. Challenges include determination of the optimal level of D1R stimulation needed to improve cognitive performance, especially when D1R expression levels, affinity states, DA levels, and the resulting D1R occupancy by DA, are not clearly known in schizophrenia, and may display great interindividual and intraindividual variability related to cognitive states and other physiological variables. These directly affect the selection of the level of stimulation necessary to correct the underlying neurobiology. The optimal mechanism for stimulation is also unknown and could include partial or full agonism, biased agonism, or positive allosteric modulation. Furthermore, the development of D1R targeting drugs has been complicated by complexities in extrapolating from in vitro affinity determinations to in vivo use. Prior D1R-targeted drugs have been unsuccessful due to poor bioavailability, pharmacokinetics, and insufficient target engagement at tolerable doses. Newer drugs have recently become available, and these must be tested in the context of carefully designed paradigms that address methodological challenges. In this paper, we discuss how a better understanding of these challenges has shaped our proposed experimental design for testing a new D1R/D5R partial agonist, PF-06412562, renamed CVL-562.
Identifiants
pubmed: 34423843
pii: 6356403
doi: 10.1093/schbul/sbab095
pmc: PMC8781338
doi:
Substances chimiques
Dopamine Agonists
0
Receptors, Dopamine D1
0
Receptors, Dopamine D5
137750-35-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
199-210Subventions
Organisme : NIMH NIH HHS
ID : U01 MH121766
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Investigateurs
Deepak D'Souza
(D)
Vinod Srihari
(V)
Ralitza Gueorguieva
(R)
Prashant Patel
(P)
Kimberlee Forselius-Bielen
(K)
Jing Lu
(J)
Audrey Butler
(A)
Geena Fram
(G)
Yvette Afriyie-Agyemang
(Y)
Alexandria Selloni
(A)
Laura Cadavid
(L)
Sandra Gomez-Luna
(S)
Aarti Gupta
(A)
Rajiv Radhakrishnan
(R)
Ali Rashid
(A)
Ryan Aker
(R)
Philisha Abrahim
(P)
Anahita Bassir Nia
(A)
Toral Surti
(T)
Lawrence S Kegeles
(LS)
Marlene Carlson
(M)
Terry Goldberg
(T)
James Gangwisch
(J)
Erinne Benedict
(E)
Preetika Govil
(P)
Stephanie Brazis
(S)
Megan Mayer
(M)
Nathalie de la Garrigue
(N)
Natalka Fallon
(N)
Topaz Baumvoll
(T)
Sameera Abeykoon
(S)
Greg Perlman
(G)
Kelly Bobchin
(K)
Mark Elliott
(M)
Lyndsay Schmidt
(L)
Sage Rush
(S)
Allison Port
(A)
Zac Heffernan
(Z)
Nina Laney
(N)
Jenna Kantor
(J)
Thomas Hohing
(T)
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Références
Neuroscience. 2011 Dec 15;198:112-37
pubmed: 21939738
Biol Psychiatry. 2018 Apr 15;83(8):635-637
pubmed: 29559095
Neuropharmacology. 2019 May 15;150:46-58
pubmed: 30858103
Neuropharmacology. 2007 Feb;52(2):562-75
pubmed: 17067639
Mol Pharmacol. 1983 Mar;23(2):295-302
pubmed: 6835198
Cereb Cortex. 2009 Aug;19(8):1820-34
pubmed: 19020206
Am J Psychiatry. 2006 Oct;163(10):1747-53
pubmed: 17012685
Schizophr Bull. 2007 Sep;33(5):1120-30
pubmed: 17641146
Schizophr Res. 2007 Jul;93(1-3):42-50
pubmed: 17467956
J Neurosci. 2001 May 15;21(10):3628-38
pubmed: 11331392
Biol Psychiatry. 2010 Oct 1;68(7):634-41
pubmed: 20673873
Neuropsychopharmacology. 2010 Jan;35(1):4-26
pubmed: 19812543
Clin Neuropharmacol. 1998 Nov-Dec;21(6):339-43
pubmed: 9844789
Int J Neuropsychopharmacol. 2020 May 27;23(5):287-299
pubmed: 32055822
Neuropsychopharmacology. 2021 May;46(6):1145-1151
pubmed: 33203954
J Psychopharmacol. 2012 Jun;26(6):794-805
pubmed: 21768159
Schizophr Res. 2004 Dec 15;72(1):5-9
pubmed: 15531402
Arch Gen Psychiatry. 1987 Jul;44(7):660-9
pubmed: 3606332
Psychopharmacology (Berl). 2001 Jun;155(4):330-7
pubmed: 11441422
Neuropsychopharmacology. 2015 Jan;40(2):446-53
pubmed: 25074637
Neuropsychopharmacology. 2020 Apr;45(5):780-785
pubmed: 31962344
J Neurosci. 1997 Nov 1;17(21):8528-35
pubmed: 9334425
Br J Psychiatry. 2014 Jun;204(6):420-9
pubmed: 25029687
Arch Gen Psychiatry. 1988 Jul;45(7):609-15
pubmed: 3382320
Psychopharmacology (Berl). 2001 Jun;155(4):338-47
pubmed: 11441423
Schizophr Res. 2009 Mar;108(1-3):78-84
pubmed: 19056247
J Pharmacol Exp Ther. 1996 Mar;276(3):1022-9
pubmed: 8786531
Arch Gen Psychiatry. 1990 Feb;47(2):190-1
pubmed: 2405808
Behav Pharmacol. 2003 Mar;14(2):111-20
pubmed: 12658071
J Clin Exp Neuropsychol. 2009 Oct;31(7):848-59
pubmed: 19142774
Philos Trans R Soc Lond B Biol Sci. 1996 Oct 29;351(1346):1495-503
pubmed: 8941961
J Neurosci. 2002 May 1;22(9):3708-19
pubmed: 11978847
Synapse. 2000 Aug;37(2):125-45
pubmed: 10881034
Life Sci. 2010 May 22;86(21-22):814-8
pubmed: 20361984
Am J Psychiatry. 1999 Oct;156(10):1580-9
pubmed: 10518170
Psychopharmacology (Berl). 1995 Oct;121(3):317-22
pubmed: 8584612
Neurology. 1975 Aug;25(8):701-4
pubmed: 1171402
Arch Gen Psychiatry. 2002 Jan;59(1):25-30
pubmed: 11779278
Biol Psychiatry. 2006 Sep 15;60(6):621-9
pubmed: 16580642
Schizophr Bull. 1997;23(3):437-58
pubmed: 9327508
Neurodegener Dis. 2018;18(5-6):262-269
pubmed: 30453303
CNS Drug Rev. 2001 Winter;7(4):399-414
pubmed: 11830757
Nat Commun. 2018 Feb 14;9(1):674
pubmed: 29445200
Nat Rev Drug Discov. 2010 May;9(5):373-86
pubmed: 20431569
Mol Psychiatry. 2021 Feb;26(2):645-655
pubmed: 30532019
J Biol Chem. 1982 Jun 10;257(11):6351-61
pubmed: 6176582
J Cereb Blood Flow Metab. 2012 Jan;32(1):127-36
pubmed: 21878947
J Med Chem. 1995 Sep 1;38(18):3445-7
pubmed: 7658429
Curr Opin Investig Drugs. 2001 Nov;2(11):1582-91
pubmed: 11763161
J Psychopharmacol. 2016 May;30(5):428-35
pubmed: 26966119
Nature. 1997 Feb 13;385(6617):634-6
pubmed: 9024661
Med Res Rev. 1985 Apr-Jun;5(2):145-229
pubmed: 3887065
Biochem Pharmacol. 2012 Jan 15;83(2):193-8
pubmed: 21945484
Pharmacol Ther. 2012 Jan;133(1):19-25
pubmed: 21839776
J Cereb Blood Flow Metab. 2011 Jan;31(1):293-304
pubmed: 20571519
Eur J Pharmacol. 1992 Mar 24;213(2):259-67
pubmed: 1355737
Crit Rev Neurobiol. 2000;14(1):1-21
pubmed: 11253953
Front Pharmacol. 2017 Oct 06;8:666
pubmed: 29056909
Nature. 1995 Aug 17;376(6541):572-5
pubmed: 7637804
Int J Neuropsychopharmacol. 2003 Dec;6(4):361-70
pubmed: 14604451
Neuroscience. 2000;96(3):451-74
pubmed: 10717427
CNS Drug Rev. 2001 Fall;7(3):305-16
pubmed: 11607045
Neuropsychopharmacology. 2003 Sep;28(9):1703-11
pubmed: 12813475
Science. 2000 Mar 17;287(5460):2020-2
pubmed: 10720329
Schizophr Res. 2000 May 25;43(1):47-55
pubmed: 10828414
J Nucl Med. 1996 Jul;37(7):1242-56
pubmed: 8965206
Prog Neurobiol. 2004 Sep;74(1):1-58
pubmed: 15381316
J Nucl Med. 2010 Mar;51(3):496-7
pubmed: 20150251
Arch Gen Psychiatry. 1994 Feb;51(2):124-31
pubmed: 7905258
Am J Psychiatry. 2002 May;159(5):761-7
pubmed: 11986129
J Neurophysiol. 1994 Feb;71(2):515-28
pubmed: 7909839
Psychopharmacology (Berl). 2013 Jul;228(1):167-74
pubmed: 23460265
Biol Psychiatry. 1999 Sep 1;46(5):681-8
pubmed: 10472420
Biol Psychiatry. 2020 Apr 1;87(7):678-685
pubmed: 31668477
Psychopharmacology (Berl). 2008 Sep;200(1):117-27
pubmed: 18600316
Cereb Cortex. 1998 Jun;8(4):321-45
pubmed: 9651129
J Pharmacol Exp Ther. 2010 May;333(2):533-9
pubmed: 20103586
J Neural Transm. 1987;68(1-2):41-50
pubmed: 2949059
Front Pharmacol. 2020 Jul 07;11:1005
pubmed: 32733245
J Med Chem. 2014 Aug 28;57(16):6887-96
pubmed: 24697360
JAMA Psychiatry. 2015 Apr;72(4):316-24
pubmed: 25651194
Eur J Pharmacol. 1978 Sep 1;51(1):19-28
pubmed: 29762
Mol Psychiatry. 2008 Aug;13(8):821-7
pubmed: 18317466
Neurology. 1989 Jun;39(6):856-8
pubmed: 2725884
Neuron. 2012 Oct 4;76(1):223-39
pubmed: 23040817
Eur J Pharmacol. 1989 Jul 4;166(1):111-3
pubmed: 2572425
Am J Physiol Renal Physiol. 2014 Jul 1;307(1):F116-21
pubmed: 24808534
J Neurosci. 1991 Jul;11(7):1907-17
pubmed: 2066768
J Pharmacol Exp Ther. 2007 Jan;320(1):1-13
pubmed: 16803859
Prog Mol Biol Transl Sci. 2014;122:211-31
pubmed: 24484703
J Pharmacol Exp Ther. 1997 Apr;281(1):597-603
pubmed: 9103549
Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6917-22
pubmed: 11381111
J Med Chem. 1994 Jul 22;37(15):2453-60
pubmed: 7914538
J Neurosci. 2007 Jul 25;27(30):8080-7
pubmed: 17652599
J Med Chem. 2018 Dec 27;61(24):11384-11397
pubmed: 30431269
Clin Pharmacol Drug Dev. 2021 Apr;10(4):393-403
pubmed: 33029934
Mol Imaging Biol. 2007 May-Jun;9(3):117-25
pubmed: 17473957
Nature. 1991 Apr 18;350(6319):614-9
pubmed: 1826762
Schizophr Bull. 2011 May;37(3):484-92
pubmed: 21505115
J Pharmacol Exp Ther. 1992 Jul;262(1):383-93
pubmed: 1352553
Neuroimage. 2006 May 15;31(1):139-52
pubmed: 16469510
Psychiatry Res. 2000 Nov 20;100(1):1-11
pubmed: 11090720
Neurology. 1985 Oct;35(10):1506-9
pubmed: 3875807
Brain Res. 1996 May 6;719(1-2):129-37
pubmed: 8782872
Neuropsychopharmacology. 2010 Feb;35(3):806-17
pubmed: 19956086
Mol Psychiatry. 2020 Sep;25(9):2086-2100
pubmed: 30120413
Psychiatry Res. 2008 Jul 15;163(2):171-82
pubmed: 18504119
Psychopharmacology (Berl). 2014 Oct;231(21):4231-40
pubmed: 24781514
Arch Gen Psychiatry. 1986 Feb;43(2):114-24
pubmed: 3947207
Sci Rep. 2020 Feb 13;10(1):2542
pubmed: 32054879
Psychopharmacology (Berl). 1994 Oct;116(2):143-51
pubmed: 7862943
J Psychopharmacol. 2019 Oct;33(10):1237-1247
pubmed: 31264510
J Cereb Blood Flow Metab. 2007 Oct;27(10):1733-41
pubmed: 17311076
Science. 1979 Aug 31;205(4409):929-32
pubmed: 112679
Obesity (Silver Spring). 2007 Jul;15(7):1717-31
pubmed: 17636090
Brain. 2018 Jul 1;141(7):2213-2224
pubmed: 29860329
ACS Chem Neurosci. 2020 Feb 19;11(4):560-566
pubmed: 31971364
Nature. 1995 Nov 9;378(6553):180-2
pubmed: 7477319
Biol Psychiatry. 2017 May 15;81(10):874-885
pubmed: 28434616
Mol Psychiatry. 2014 Mar;19(3):302-10
pubmed: 23439486
Biol Psychiatry. 2009 Jun 15;65(12):1024-31
pubmed: 19251247
Physiol Behav. 2002 Dec;77(4-5):513-7
pubmed: 12526992
J Cereb Blood Flow Metab. 2007 Sep;27(9):1533-9
pubmed: 17519979