Strategies to enhance N-methyl-D-aspartate receptor-mediated neurotransmission in schizophrenia, a critical review and meta-analysis
Although hypofunction of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission is proposed to play an important role in the pathophysiology of schizophrenia, results of the clinical trials of small molecules that enhance the NMDA function are inconsistent. A meta-analysis of all the double...
Saved in:
Published in | Current pharmaceutical design Vol. 16; no. 5; p. 522 |
---|---|
Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United Arab Emirates
01.02.2010
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Abstract | Although hypofunction of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission is proposed to play an important role in the pathophysiology of schizophrenia, results of the clinical trials of small molecules that enhance the NMDA function are inconsistent. A meta-analysis of all the double-blind, placebo-controlled studies in patients with schizophrenia was performed to examine their efficacy on different symptom domains, the dose-response, the effects of concomitant antipsychotics, and their side effects. About eight hundred subjects from 26 studies were included in current meta-analysis. Overall, the NMDA-enhancing molecules are effective in most schizophrenic symptom domains with the effect size (ES) of total psychopathology of 0.40 (p<1 x 10(-4)). The ES of clinical efficacy of the symptom domains were in the order of depressive (0.40, p=3 x 10(-4)), negative (0.38, p<1 x 10(-4)), cognitive (0.28, p=2 x 10(-3)), positive symptom (0.26, p=0.0006), and general psychopathology (0.26, p=0.006). Glycine, D-serine, and sarcosine treatments significantly improved multiple symptom domains, whereas D-cycloserine did not improve any symptom domain. Moderator analysis revealed that glycine, D-serine and sarcosine are better than D-cycloserine in improving the overall psychopathology. Patients receiving risperidone or olanzapine, but not clozapine, improved. No significant side effect or safety concern was noted. In addition to testing more lead compounds, long-term trials are required to determine their functional improvement capacity. Other drug targets that may enhance NMDA neurotransmission more than the molecules tested so far need to be explored. |
---|---|
AbstractList | Although hypofunction of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission is proposed to play an important role in the pathophysiology of schizophrenia, results of the clinical trials of small molecules that enhance the NMDA function are inconsistent. A meta-analysis of all the double-blind, placebo-controlled studies in patients with schizophrenia was performed to examine their efficacy on different symptom domains, the dose-response, the effects of concomitant antipsychotics, and their side effects. About eight hundred subjects from 26 studies were included in current meta-analysis. Overall, the NMDA-enhancing molecules are effective in most schizophrenic symptom domains with the effect size (ES) of total psychopathology of 0.40 (p<1 x 10(-4)). The ES of clinical efficacy of the symptom domains were in the order of depressive (0.40, p=3 x 10(-4)), negative (0.38, p<1 x 10(-4)), cognitive (0.28, p=2 x 10(-3)), positive symptom (0.26, p=0.0006), and general psychopathology (0.26, p=0.006). Glycine, D-serine, and sarcosine treatments significantly improved multiple symptom domains, whereas D-cycloserine did not improve any symptom domain. Moderator analysis revealed that glycine, D-serine and sarcosine are better than D-cycloserine in improving the overall psychopathology. Patients receiving risperidone or olanzapine, but not clozapine, improved. No significant side effect or safety concern was noted. In addition to testing more lead compounds, long-term trials are required to determine their functional improvement capacity. Other drug targets that may enhance NMDA neurotransmission more than the molecules tested so far need to be explored. |
Author | Lin, Pao-Yen Tsai, Guochuan E |
Author_xml | – sequence: 1 givenname: Guochuan E surname: Tsai fullname: Tsai, Guochuan E email: etsai@labiomed.org organization: Department of Psychiatry, Harbor-UCLA Medical Center, HH2121, 1000 W. Carson Street, Torrance, CA 90509, USA. etsai@labiomed.org – sequence: 2 givenname: Pao-Yen surname: Lin fullname: Lin, Pao-Yen |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19909229$$D View this record in MEDLINE/PubMed |
BookMark | eNo1kE9LAzEUxIMo1la_gAfJB3A1L5vuNkepf6HoQT2Xt9kXN7LNLkmq1LMf3IB6GpgZfjAzZft-8MTYKYgLCbW6hHIBFUgQtRZlBWou99gRLOqyUHJRTdg0xnchQGpQh2wCWgstpT5i388pYKI3R5GngZPv0Bvij8WGUrfri-sC44gh5Q4PZGhMQ8hZ67LRck_bMGSAjxsXoxs8d55H07mvYewCeYfnHLkJLjmDfQZ8OPrk6Fue8Vigx34XXTxmBxb7SCd_OmOvtzcvy_ti9XT3sLxaFc1cqlS0WlbWCBAGoSypaRtLSAIqpZSRbR5L2lqrsG7rprFCQVUZDbZZKKMtkZyxs1_uuG3yhvUY3AbDbv1_h_wBhoVmxA |
CitedBy_id | crossref_primary_10_1097_JCP_0000000000000073 crossref_primary_10_1016_j_euroneuro_2012_09_008 crossref_primary_10_1016_j_neuropharm_2011_04_010 crossref_primary_10_1177_0269881113512909 crossref_primary_10_3928_00485713_20180308_01 crossref_primary_10_1007_s10967_012_1860_5 crossref_primary_10_3389_fnins_2021_641047 crossref_primary_10_1038_npp_2011_181 crossref_primary_10_1016_j_psc_2016_01_005 crossref_primary_10_1155_2014_859735 crossref_primary_10_1016_j_pbb_2023_173586 crossref_primary_10_1007_s11920_014_0439_y crossref_primary_10_1038_nrd3893 crossref_primary_10_1016_j_biopsych_2010_11_030 crossref_primary_10_1016_j_biopsych_2010_05_034 crossref_primary_10_17116_jnevro201711761126_132 crossref_primary_10_1007_s00213_010_2023_4 crossref_primary_10_1080_17425255_2021_1885648 crossref_primary_10_1159_000493399 crossref_primary_10_3390_nu7105427 crossref_primary_10_1016_j_jneumeth_2011_08_040 crossref_primary_10_1016_j_neuint_2011_08_017 crossref_primary_10_1080_14656566_2018_1543409 crossref_primary_10_1007_s15202_015_0941_4 crossref_primary_10_1177_0269881114563634 crossref_primary_10_1016_j_psiq_2010_07_002 crossref_primary_10_1111_bph_13919 crossref_primary_10_3109_15622975_2015_1117654 crossref_primary_10_1038_npjschz_2016_3 crossref_primary_10_1186_s13030_017_0101_0 crossref_primary_10_3390_molecules24203709 crossref_primary_10_1016_j_biopsych_2017_08_022 crossref_primary_10_1254_fpj_136_128 crossref_primary_10_1176_appi_ajp_2020_20101481 crossref_primary_10_1073_pnas_1304308110 crossref_primary_10_1016_j_ejphar_2012_04_013 crossref_primary_10_1007_s12035_017_0555_x crossref_primary_10_1016_j_bcp_2024_116376 crossref_primary_10_1016_j_euroneuro_2013_05_008 crossref_primary_10_1093_schbul_sbv135 crossref_primary_10_1016_j_neuropharm_2011_06_029 crossref_primary_10_1038_mp_2013_80 crossref_primary_10_1016_j_bbr_2014_06_012 crossref_primary_10_1016_j_neubiorev_2015_01_016 crossref_primary_10_1038_s41537_018_0064_6 crossref_primary_10_2165_11586650_000000000_00000 crossref_primary_10_3390_ph3103240 crossref_primary_10_1016_j_biopsych_2011_01_026 crossref_primary_10_1001_jamanetworkopen_2020_24335 crossref_primary_10_1016_j_schres_2020_05_050 crossref_primary_10_1016_j_psychres_2022_114926 crossref_primary_10_1126_scitranslmed_3002804 crossref_primary_10_1371_journal_pone_0062438 crossref_primary_10_1093_schbul_sbs076 crossref_primary_10_1017_neu_2018_32 crossref_primary_10_3389_fpsyt_2021_514579 crossref_primary_10_3390_molecules28104108 crossref_primary_10_1007_s12017_014_8319_5 crossref_primary_10_1016_j_euroneuro_2012_03_006 crossref_primary_10_1097_JCP_0000000000001388 crossref_primary_10_1155_2014_104920 crossref_primary_10_1016_j_neuroscience_2015_03_039 crossref_primary_10_2165_11634390_000000000_00000 crossref_primary_10_1016_j_schres_2017_02_027 crossref_primary_10_1016_j_biopsych_2013_12_003 crossref_primary_10_1016_j_neuropharm_2011_01_030 crossref_primary_10_1016_j_neuropharm_2019_107681 crossref_primary_10_31887_DCNS_2010_12_3_jcoyle crossref_primary_10_1038_mp_2012_47 crossref_primary_10_1146_annurev_pharmtox_010909_105851 crossref_primary_10_1177_0269881120908016 crossref_primary_10_1007_s00406_013_0399_y crossref_primary_10_1016_j_biopsych_2016_04_007 crossref_primary_10_1016_j_ddstr_2011_09_002 crossref_primary_10_1016_j_euroneuro_2013_09_011 crossref_primary_10_1162_NECO_a_00944 crossref_primary_10_9740_mhc_2016_11_266 crossref_primary_10_1016_j_pharmthera_2018_08_010 crossref_primary_10_1080_14728222_2021_1849144 crossref_primary_10_3389_fpsyt_2019_00025 crossref_primary_10_1016_j_jpsychires_2013_12_007 crossref_primary_10_1007_s00213_011_2247_y crossref_primary_10_4155_fmc_13_118 crossref_primary_10_1038_npp_2016_2 crossref_primary_10_1038_mp_2015_68 crossref_primary_10_3390_nu14235142 crossref_primary_10_5402_2012_427267 crossref_primary_10_1007_s40501_016_0075_8 crossref_primary_10_1177_0269881118822157 crossref_primary_10_1017_neu_2015_1 crossref_primary_10_1016_j_ejphar_2012_02_033 crossref_primary_10_3390_nu11092205 crossref_primary_10_1038_s41598_021_02040_5 crossref_primary_10_1038_s41398_017_0060_z crossref_primary_10_1038_srep38321 crossref_primary_10_1016_j_neubiorev_2010_10_005 crossref_primary_10_1016_j_schres_2012_11_006 crossref_primary_10_1111_j_1476_5381_2011_01638_x crossref_primary_10_1016_j_neulet_2011_06_011 crossref_primary_10_1016_j_eururo_2012_01_044 crossref_primary_10_1016_j_neuropharm_2011_03_013 crossref_primary_10_1111_adb_12577 crossref_primary_10_1007_s00228_018_2595_1 crossref_primary_10_1517_14728222_2014_934225 crossref_primary_10_1016_j_euroneuro_2013_08_009 crossref_primary_10_3762_bjnano_15_42 crossref_primary_10_1016_j_jpsychires_2024_05_004 crossref_primary_10_1111_bph_12518 crossref_primary_10_1016_j_euroneuro_2014_08_014 crossref_primary_10_1016_j_pbb_2011_03_023 crossref_primary_10_1016_j_coph_2014_12_004 crossref_primary_10_1038_s41598_023_49983_5 crossref_primary_10_1073_pnas_1512064112 crossref_primary_10_1016_j_brainres_2020_147202 crossref_primary_10_1111_pcn_12823 crossref_primary_10_1038_s41537_022_00265_5 crossref_primary_10_1093_schbul_sbs069 crossref_primary_10_1016_j_biopsych_2013_02_020 crossref_primary_10_1016_j_biopsych_2012_07_013 crossref_primary_10_1080_15332985_2014_894487 crossref_primary_10_1007_s00702_019_02041_9 crossref_primary_10_1016_j_schres_2015_11_015 crossref_primary_10_1017_S1461145711001386 crossref_primary_10_2139_ssrn_3957491 crossref_primary_10_1177_0269881117741766 crossref_primary_10_1016_j_jpsychires_2014_12_007 crossref_primary_10_3389_fpsyt_2018_00537 crossref_primary_10_3389_fpsyt_2021_742058 crossref_primary_10_1177_2045125311400779 crossref_primary_10_1007_s12264_021_00740_6 crossref_primary_10_1186_s13063_021_05890_6 crossref_primary_10_1007_s00702_020_02292_x crossref_primary_10_1016_j_bcp_2011_02_003 crossref_primary_10_1016_j_bmc_2011_11_038 crossref_primary_10_3389_fpsyt_2019_00601 crossref_primary_10_1002_jbt_22022 crossref_primary_10_1016_j_tetasy_2012_10_005 crossref_primary_10_1038_s41380_023_02312_8 crossref_primary_10_1586_ecp_12_57 crossref_primary_10_1016_j_neuint_2012_01_004 crossref_primary_10_1093_schizbullopen_sgae004 crossref_primary_10_1016_j_schres_2016_10_027 crossref_primary_10_1186_s13063_017_1908_5 crossref_primary_10_1080_15504263_2018_1549764 crossref_primary_10_1002_mds_25306 crossref_primary_10_3389_fpsyt_2014_00032 crossref_primary_10_1016_S2215_0366_15_00098_X crossref_primary_10_1177_0269881120965937 crossref_primary_10_1016_j_gene_2015_05_011 crossref_primary_10_2174_1570178620666230518145740 crossref_primary_10_1186_s12888_017_1410_3 crossref_primary_10_1007_s00213_011_2330_4 crossref_primary_10_1080_15622975_2016_1183043 crossref_primary_10_1016_j_psychres_2016_05_019 crossref_primary_10_1038_s41380_024_02631_4 crossref_primary_10_1016_j_nucmedbio_2012_02_008 crossref_primary_10_1017_S0033291717001271 crossref_primary_10_1097_NMD_0000000000000782 crossref_primary_10_1155_2017_2875904 crossref_primary_10_1016_j_jpsychires_2012_03_015 crossref_primary_10_1093_ijnp_pyv102 crossref_primary_10_1016_j_nbd_2011_10_006 crossref_primary_10_1177_0269881116672342 crossref_primary_10_1016_S2215_0366_16_30354_6 crossref_primary_10_1038_s41380_022_01649_w crossref_primary_10_1021_jm400383w crossref_primary_10_1586_17512433_2015_1040393 crossref_primary_10_1007_s00213_014_3738_4 crossref_primary_10_1038_npp_2015_84 crossref_primary_10_1038_srep37261 crossref_primary_10_1007_s11357_023_00970_8 crossref_primary_10_1016_j_biopsych_2019_04_031 crossref_primary_10_1093_schizbullopen_sgae013 crossref_primary_10_1016_j_genhosppsych_2014_02_010 crossref_primary_10_1016_j_neuropharm_2010_07_023 crossref_primary_10_1007_s00406_014_0534_4 crossref_primary_10_1097_YCO_0b013e32835035b2 crossref_primary_10_1038_npp_2014_4 crossref_primary_10_1517_17460441_2012_724057 |
ContentType | Journal Article |
DBID | CGR CUY CVF ECM EIF NPM |
DOI | 10.2174/138161210790361452 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
Discipline | Pharmacy, Therapeutics, & Pharmacology |
EISSN | 1873-4286 |
ExternalDocumentID | 19909229 |
Genre | Meta-Analysis Review Research Support, Non-U.S. Gov't Journal Article |
GroupedDBID | --- .5. 0R~ 29F 36B 3V. 4.4 53G 5GY 69Q 7X7 88E 8AO 8FI 8FJ 8R4 8R5 AAEGP ABEEF ABJNI ABUWG ABVDF ACGFO ACGFS ACITR ACIWK ACPRK ADBBV AENEX AFKRA AFRAH AFUQM AGJNZ AHMBA ALIPV ALMA_UNASSIGNED_HOLDINGS ANTIV BENPR BPHCQ BVXVI C1A CCPQU CGR CS3 CUY CVF DU5 EBS ECM EIF EJD F5P FYUFA GH2 HMCUK HZ~ IPNFZ KCGFV KFI M1P NPM O9- P2P PQQKQ PROAC PSQYO Q2X RIG UKHRP |
ID | FETCH-LOGICAL-b524t-d926fc010ca133ebdbfeae016444c2d873e9fff4a7d7bbf04166c91fb84c9fee2 |
IngestDate | Sat Sep 28 08:37:55 EDT 2024 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 5 |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-b524t-d926fc010ca133ebdbfeae016444c2d873e9fff4a7d7bbf04166c91fb84c9fee2 |
PMID | 19909229 |
ParticipantIDs | pubmed_primary_19909229 |
PublicationCentury | 2000 |
PublicationDate | 2010-02-01 |
PublicationDateYYYYMMDD | 2010-02-01 |
PublicationDate_xml | – month: 02 year: 2010 text: 2010-02-01 day: 01 |
PublicationDecade | 2010 |
PublicationPlace | United Arab Emirates |
PublicationPlace_xml | – name: United Arab Emirates |
PublicationTitle | Current pharmaceutical design |
PublicationTitleAlternate | Curr Pharm Des |
PublicationYear | 2010 |
SSID | ssj0012914 |
Score | 2.4623005 |
SecondaryResourceType | review_article |
Snippet | Although hypofunction of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission is proposed to play an important role in the pathophysiology of... |
SourceID | pubmed |
SourceType | Index Database |
StartPage | 522 |
SubjectTerms | Amino Acids - pharmacology Amino Acids - therapeutic use Animals Antipsychotic Agents - pharmacology Antipsychotic Agents - therapeutic use Dose-Response Relationship, Drug Drug Therapy, Combination Glycine - therapeutic use Humans Models, Neurological Randomized Controlled Trials as Topic Receptors, N-Methyl-D-Aspartate - agonists Schizophrenia - drug therapy Schizophrenic Psychology Synaptic Transmission - drug effects |
Title | Strategies to enhance N-methyl-D-aspartate receptor-mediated neurotransmission in schizophrenia, a critical review and meta-analysis |
URI | https://www.ncbi.nlm.nih.gov/pubmed/19909229 |
Volume | 16 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwELa2cOGCKM_SFs0B9cIaiOO8jqg8KgTVHrZSOVW2Y2uRaLJis4dyrPjhzMTObrJbEHCJVnGUjfJ9Gc-MZz4z9lwak8VGal4KUXJpEvzmZOx4msvCWRG5RFFC__NpenImP54n56PRda9qadnol-bHjX0l_4MqnkNcqUv2H5Bd3RRP4G_EF4-IMB7_CuNOWtbLNNhq1tb_o220-Pq_8bdcob2gxXbaG4XqV-rvvG0VITezVbJsaKpCqBeh5HHRr8FrKztfmG4zhNDlQpl2_APFVdAz6fu3ndzTfDZIlZeDOpHpwu-B_WFZm9kSDcyqG-KTVzSYqJp_CT1qISNBi-mr6g7rrWiexRzjmnRgZtMenZKezUx8Y_KmLadYidIKtLJJKmdZgZNtJJPBxYjH_LJFN8JptRA-e_Ln0Q197W5oh-1kOdnIU8r3hHUoUUTSt1rR47zafphWdNbfYCMwaR2U6T12N0QW8MbTZJeNbHWfHU08EFdjmK477RZjOILJWrT86gH7ueYSNDUELsFNXIItLsEWl-BrBQMujUFBxyTwTAJkEgyY9JCdvX83PT7hYYcOrhMhG14WInUGKWBUFMdWl9pZZUm1TUojSqSBLZxzUmVlprV7jd5_aorI6VwaNAVWPGK3qrqyTxgIamoucUIonMIgWuUxhf5SaW01Op16jz32b_di7mVYLrr3_vS3I_vszpqfB-y2w-_eHqIT2ehnLc6_ACVad7Y |
link.rule.ids | 786 |
linkProvider | National Library of Medicine |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Strategies+to+enhance+N-methyl-D-aspartate+receptor-mediated+neurotransmission+in+schizophrenia%2C+a+critical+review+and+meta-analysis&rft.jtitle=Current+pharmaceutical+design&rft.au=Tsai%2C+Guochuan+E&rft.au=Lin%2C+Pao-Yen&rft.date=2010-02-01&rft.eissn=1873-4286&rft.volume=16&rft.issue=5&rft.spage=522&rft_id=info:doi/10.2174%2F138161210790361452&rft_id=info%3Apmid%2F19909229&rft_id=info%3Apmid%2F19909229&rft.externalDocID=19909229 |