Abstract
In the central nervous system (CNS), G-protein-coupled receptors (GPCRs) are the most common targets of neuropharmacological drugs. GPCRs are activated by various neurotransmitters, which results in slow synaptic transmission. Recently, remarkable progress has been achieved in identifying genes and signaling pathways linked to the risk of psychiatric disorders. Even though the biological mechanisms governing psychiatric disorders, such as mood disorders and schizophrenia, are uncertain, GPCRs are essential in diagnosing and treating various ailments. However, due to the complicated reasons responsible for these disorders, there has been a significant decrease in the pipeline for the progression of novel psychiatric medications throughout the world. Antipsychotics and antidepressants target GPCRs, which regulate various subsequent signaling pathways and play a key role in altering brain function. The advancement of our knowledge of GPCR signaling has opened up new avenues for developing customized medications. This review summarizes the current understanding of therapeutic GPCR targets for psychiatric disorders. For patients resistant to current therapies, the future development of new drugs targeting GPCR signaling pathways is promising.
Keywords: GPCRs, psychiatric disorders, mood disorders, schizophrenia, antidepressants, risk factor.
[http://dx.doi.org/10.1111/febs.15738] [PMID: 33523596]
[http://dx.doi.org/10.1192/bjp.bp.110.080499] [PMID: 21037215]
[http://dx.doi.org/10.1097/NMD.0000000000000049] [PMID: 24284634]
[http://dx.doi.org/10.1007/s00406-005-0624-4] [PMID: 16311898]
[http://dx.doi.org/10.1016/j.biopsych.2010.05.028] [PMID: 20674602]
[http://dx.doi.org/10.1007/978-1-4939-9554-7_10]
[http://dx.doi.org/10.3389/fnbeh.2018.00157] [PMID: 30108490]
[http://dx.doi.org/10.1007/s00213-010-2096-0] [PMID: 21086114]
[http://dx.doi.org/10.3390/cells9020506] [PMID: 32102186]
[http://dx.doi.org/10.1097/WAD.0000000000000034] [PMID: 24632990]
[http://dx.doi.org/10.1016/S0361-9230(01)00523-8] [PMID: 11576760]
[http://dx.doi.org/10.1016/B978-0-12-397179-1.00010-5]
[http://dx.doi.org/10.1126/science.294.5544.1024]
[http://dx.doi.org/10.1016/0896-6273(93)90236-K] [PMID: 8427698]
[http://dx.doi.org/10.1371/journal.pone.0118510] [PMID: 25693194]
[http://dx.doi.org/10.1016/0022-510X(73)90175-5] [PMID: 4272516]
[http://dx.doi.org/10.1038/nrn3746] [PMID: 24840803]
[http://dx.doi.org/10.1177/0269881114523864] [PMID: 24554693]
[http://dx.doi.org/10.1176/jnp.8.2.223] [PMID: 9081563]
[http://dx.doi.org/10.1176/ajp.141.5.633] [PMID: 6143506]
[http://dx.doi.org/10.1176/ajp.144.7.934] [PMID: 2886063]
[http://dx.doi.org/10.1016/B978-0-12-374767-9.00006-8]
[http://dx.doi.org/10.1016/j.jclinepi.2021.02.003] [PMID: 33577987]
[http://dx.doi.org/10.4062/biomolther.2016.165] [PMID: 28035079]
[http://dx.doi.org/10.1038/s41467-017-02661-3] [PMID: 29362459]
[http://dx.doi.org/10.1126/scisignal.aal3395] [PMID: 28634209]
[http://dx.doi.org/10.3389/fendo.2012.00105] [PMID: 22952466]
[http://dx.doi.org/10.1016/S0140-6736(96)07495-8] [PMID: 9164317]
[http://dx.doi.org/10.1016/j.bbamem.2006.09.025] [PMID: 17078926]
[http://dx.doi.org/10.4135/9781412982733.n10]
[http://dx.doi.org/10.1176/appi.ajp.157.10.1552] [PMID: 11007705]
[http://dx.doi.org/10.1016/0006-3223(94)90597-5] [PMID: 7893850]
[http://dx.doi.org/10.1056/NEJMra035354] [PMID: 15282355]
[http://dx.doi.org/10.1097/00004850-199100640-00001] [PMID: 1816278]
[http://dx.doi.org/10.1016/0278-5846(92)90062-J] [PMID: 1322549]
[http://dx.doi.org/10.1016/0014-2999(89)90687-0] [PMID: 2553432]
[http://dx.doi.org/10.1016/0006-3223(90)90399-M] [PMID: 2171686]
[http://dx.doi.org/10.1002/ajmg.1320600212]
[http://dx.doi.org/10.1159/000090703] [PMID: 16397404]
[http://dx.doi.org/10.1002/ajmg.10118]
[http://dx.doi.org/10.1016/S0165-1781(99)00034-7] [PMID: 10482338]
[http://dx.doi.org/10.1097/00041444-199912000-00005] [PMID: 10697826]
[http://dx.doi.org/10.1016/j.biopsych.2005.01.030] [PMID: 15860340]
[http://dx.doi.org/10.1016/S0006-3223(97)00484-8] [PMID: 9564441]
[http://dx.doi.org/10.1523/JNEUROSCI.18-18-07394.1998] [PMID: 9736659]
[http://dx.doi.org/10.1007/BF01244944] [PMID: 1834090]
[http://dx.doi.org/10.1038/sj.npp.1300992] [PMID: 16395308]
[http://dx.doi.org/10.1016/S0006-3223(99)00189-4] [PMID: 10578452]
[http://dx.doi.org/10.1001/archpsyc.57.2.174] [PMID: 10665620]
[PMID: 1839498]
[http://dx.doi.org/10.1016/0165-6147(94)90315-8] [PMID: 7940983]
[http://dx.doi.org/10.1016/S0028-3908(02)00064-3] [PMID: 12128004]
[http://dx.doi.org/10.1001/archpsyc.56.8.705] [PMID: 10435604]
[http://dx.doi.org/10.1007/s00213-003-1530-y] [PMID: 12845409]
[http://dx.doi.org/10.1016/0024-3205(86)90248-1] [PMID: 3007903]
[PMID: 2153910]
[http://dx.doi.org/10.1016/0014-2999(88)90028-3] [PMID: 3416916]
[PMID: 2885406]
[http://dx.doi.org/10.1097/00006842-199909000-00004] [PMID: 10511011]
[http://dx.doi.org/10.1192/bjp.152.5.665] [PMID: 2844354]
[http://dx.doi.org/10.1176/ajp.136.5.675] [PMID: 219719]
[http://dx.doi.org/10.1016/0165-1781(79)90061-1] [PMID: 233157]
[http://dx.doi.org/10.1056/NEJM198509193131202] [PMID: 2993884]
[http://dx.doi.org/10.1016/0022-3956(82)90003-6] [PMID: 6821276]
[http://dx.doi.org/10.1111/j.1469-1809.1984.tb01016.x] [PMID: 6087716]
[http://dx.doi.org/10.1186/1741-7015-11-200] [PMID: 24228900]
[http://dx.doi.org/10.1007/s12035-020-01961-y] [PMID: 32700250]
[http://dx.doi.org/10.1016/j.bbi.2019.09.016] [PMID: 31550500]
[http://dx.doi.org/10.1016/j.brainres.2014.06.032]
[http://dx.doi.org/10.1192/bjo.2020.43] [PMID: 32498754]
[http://dx.doi.org/10.1007/s12035-015-9090-9] [PMID: 25598355]
[http://dx.doi.org/10.1101/cshperspect.a016303]
[http://dx.doi.org/10.1016/j.imlet.2014.03.006] [PMID: 24698730]
[http://dx.doi.org/10.3389/fncel.2015.00476] [PMID: 26733805]
[http://dx.doi.org/10.1016/j.pnpbp.2020.110139] [PMID: 33068682]
[http://dx.doi.org/10.3389/fnmol.2019.00210] [PMID: 31555091]
[http://dx.doi.org/10.1101/cshperspect.a020560] [PMID: 26354893]
[http://dx.doi.org/10.1016/j.tcb.2016.02.006] [PMID: 27004698]
[http://dx.doi.org/10.1016/S2215-0366(17)30101-3] [PMID: 28454915]
[http://dx.doi.org/10.1186/s40035-020-00221-2] [PMID: 33239064]
[http://dx.doi.org/10.1523/JNEUROSCI.3004-12.2013] [PMID: 24068827]
[http://dx.doi.org/10.1016/j.tins.2012.11.007] [PMID: 23260014]
[http://dx.doi.org/10.1007/s11427-020-1815-6] [PMID: 33068286]
[http://dx.doi.org/10.1111/cei.13119] [PMID: 29453850]
[http://dx.doi.org/10.1007/s11596-020-2193-1] [PMID: 32681244]
[http://dx.doi.org/10.1016/j.molmed.2018.11.005] [PMID: 30578090]
[http://dx.doi.org/10.1016/j.biopha.2022.112668] [PMID: 35104696]
[http://dx.doi.org/10.1016/j.jad.2019.05.009] [PMID: 31082627]
[http://dx.doi.org/10.1016/j.lfs.2020.118582] [PMID: 33058911]
[http://dx.doi.org/10.1016/j.bbi.2017.03.002] [PMID: 28263786]
[http://dx.doi.org/10.1038/cmi.2015.95] [PMID: 26549800]
[http://dx.doi.org/10.1038/s41577-019-0165-0] [PMID: 31036962]
[http://dx.doi.org/10.1016/j.bbi.2014.04.007] [PMID: 24859041]
[http://dx.doi.org/10.1016/S1734-1140(13)71527-5] [PMID: 24553014]
[http://dx.doi.org/10.2174/13894501113146660214] [PMID: 24020976]
[http://dx.doi.org/10.1017/neu.2016.69] [PMID: 28112061]
[http://dx.doi.org/10.3389/fncel.2015.00268] [PMID: 26217190]
[http://dx.doi.org/10.1038/npp.2016.199] [PMID: 27629368]
[http://dx.doi.org/10.1016/j.it.2007.01.005] [PMID: 17276138]
[http://dx.doi.org/10.3389/fnins.2015.00259] [PMID: 26283900]
[http://dx.doi.org/10.1007/s00213-003-1582-z] [PMID: 12955285]
[PMID: 22246848]
[http://dx.doi.org/10.1007/s10571-006-9062-8] [PMID: 16773445]
[http://dx.doi.org/10.1002/ajmg.b.20020]
[http://dx.doi.org/10.1038/sj.mp.4001556] [PMID: 15289815]
[http://dx.doi.org/10.1021/jm0002432] [PMID: 11170639]
[http://dx.doi.org/10.2174/1568007024606249] [PMID: 12769625]
[http://dx.doi.org/10.1176/ajp.156.1.72] [PMID: 9892300]
[http://dx.doi.org/10.1038/npp.1993.32] [PMID: 8512620]
[PMID: 8742799]
[http://dx.doi.org/10.1093/schbul/sbp006] [PMID: 19325164]
[http://dx.doi.org/10.3389/fnbeh.2011.00047] [PMID: 21847377]
[http://dx.doi.org/10.3389/fnbeh.2014.00188] [PMID: 24904339]
[http://dx.doi.org/10.1016/S1471-1931(00)00027-6] [PMID: 11052223]
[http://dx.doi.org/10.1016/0006-8993(88)91217-6] [PMID: 2464402]
[http://dx.doi.org/10.1371/journal.pone.0090134] [PMID: 24587241]
[http://dx.doi.org/10.1111/j.1471-4159.1991.tb08257.x] [PMID: 1713612]
[http://dx.doi.org/10.1016/j.pneurobio.2007.05.001] [PMID: 17646043]
[http://dx.doi.org/10.1038/nn1987] [PMID: 17934457]
[http://dx.doi.org/10.1038/nn.3239] [PMID: 23064379]
[http://dx.doi.org/10.1016/0166-2236(89)90074-X] [PMID: 2479133]
[http://dx.doi.org/10.1177/155005941004100204] [PMID: 20521487]
[http://dx.doi.org/10.3390/ijms20133207] [PMID: 31261897]
[http://dx.doi.org/10.1124/jpet.117.242925] [PMID: 28851764]
[http://dx.doi.org/10.1016/j.brainres.2017.05.031] [PMID: 28583861]
[http://dx.doi.org/10.1046/j.1471-4159.2003.02067.x] [PMID: 14622123]
[http://dx.doi.org/10.1073/pnas.0308618100] [PMID: 14983054] [PMCID: PMC356995]
[http://dx.doi.org/10.3390/molecules23082087] [PMID: 30127324]
[http://dx.doi.org/10.1007/s00213-006-0621-y] [PMID: 17242925]
[http://dx.doi.org/10.1007/s00213-009-1611-7] [PMID: 19641901]
[http://dx.doi.org/10.1093/ijnp/pyv111] [PMID: 26428352]
[http://dx.doi.org/10.1016/j.euroneuro.2015.01.006] [PMID: 25656272]
[http://dx.doi.org/10.1016/j.pharep.2018.04.009] [PMID: 30144663]
[http://dx.doi.org/10.1016/j.bbr.2020.112769] [PMID: 32535184]
[PMID: 27512008]
[http://dx.doi.org/10.1038/sj.npp.1300686] [PMID: 15702136]
[http://dx.doi.org/10.1016/S0028-3908(03)00138-2] [PMID: 12842122]
[http://dx.doi.org/10.1038/npp.2012.18] [PMID: 22373941]
[http://dx.doi.org/10.1016/j.biopsych.2006.05.015] [PMID: 16934772]
[http://dx.doi.org/10.1016/S0006-3223(01)01171-4] [PMID: 11600104]
[http://dx.doi.org/10.1111/j.1460-9568.2011.07893.x] [PMID: 22050612]
[http://dx.doi.org/10.1007/s12031-015-0536-3] [PMID: 25820671]
[http://dx.doi.org/10.1097/00008877-200212000-00005] [PMID: 12478214]
[http://dx.doi.org/10.1038/sj.bjp.0704240] [PMID: 11522598]
[http://dx.doi.org/10.1016/j.neulet.2003.10.040] [PMID: 14729225]
[http://dx.doi.org/10.1016/j.brainresbull.2005.05.025] [PMID: 16140163]
[http://dx.doi.org/10.1124/pr.118.016790] [PMID: 30914442]
[http://dx.doi.org/10.1124/jpet.106.104463] [PMID: 16803859]
[http://dx.doi.org/10.1038/nrd3954] [PMID: 23411724]
[http://dx.doi.org/10.1038/nrd.2017.229] [PMID: 29302067]
[http://dx.doi.org/10.1177/0192623312464311] [PMID: 23085982]
[http://dx.doi.org/10.1124/mol.117.110890] [PMID: 29326242]
[http://dx.doi.org/10.1007/978-3-642-66612-4_3]
[http://dx.doi.org/10.1124/pr.114.009944] [PMID: 25527701]
[http://dx.doi.org/10.1017/S1461145712001496] [PMID: 23719026]
[http://dx.doi.org/10.1046/j.1471-4159.2001.00201.x] [PMID: 11238742]
[http://dx.doi.org/10.2217/npy.11.12]
[http://dx.doi.org/10.1038/s41594-018-0180-z] [PMID: 30723326]
[http://dx.doi.org/10.1016/j.cell.2016.12.033] [PMID: 28129538]
[http://dx.doi.org/10.1016/j.cell.2018.01.001] [PMID: 29398112]
[http://dx.doi.org/10.1038/s41594-018-0116-7] [PMID: 30127358]
[http://dx.doi.org/10.1126/science.1249489]
[http://dx.doi.org/10.1016/j.ddtec.2012.10.007] [PMID: 24050278]
[http://dx.doi.org/10.1038/nrd4052] [PMID: 23903222]
[http://dx.doi.org/10.1016/0006-2952(83)90679-2] [PMID: 6311215]
[http://dx.doi.org/10.1111/j.1476-5381.1983.tb11031.x] [PMID: 6317114]
[http://dx.doi.org/10.1021/acsptsci.0c00006] [PMID: 32296764]
[http://dx.doi.org/10.1016/j.cellsig.2018.01.002] [PMID: 29329779]
[http://dx.doi.org/10.1073/pnas.1705768114]
[http://dx.doi.org/10.1126/scitranslmed.aal3447] [PMID: 28566424]
[http://dx.doi.org/10.1038/s41467-017-00357-2] [PMID: 28874659]