Table 3 Candidate drugs under development

From: G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders

Drug

Structure

Indication

Phase status

NCT

Targets (protein short names)

Mechanism

Ki (nM)

Reference

Resveratrol

Alzheimer’s disease;

schizophrenia;

Parkinson’s disease;

depression

1;

2;

2;

4

NCT01504854;

NCT02062190;

NCT03384329;

NCT03095105;

NCT03093389;

NCT03094156;

NCT03097211

Mel-1A-R

/

/

808

Mel-1B-R

/

/

SGS-742

Alzheimer’s disease;

schizophrenia;

attention deficit hyperactivity disorder

2

NCT00093951

GABBR1

/

/

/

GABBR2

/

/

SUVN-502

View full size image

Alzheimer’s disease

2

NCT02580305

5-HT-6

/

/

/

Nabilone

Alzheimer’s disease

3

NCT02351882

CB-R

Agonist

/

349

CB-2

Agonist

/

Caffeine

View full size image

Alzheimer’s disease

3

NCT04570085

adenosine receptors

/

/

350

5-HT-1

Regulator

Velusetrag

Alzheimer’s disease

1

NCT01467726

5-HT-4

/

/

/

Brexpiprazole

Alzheimer’s disease

3

NCT03620981

DRD2

Partial Agonist

/

354

Prazosin

Alzheimer’s disease

3

NCT03710642

ADRA1A

Antagonist

/

809

CB-2

/

/

GPR12

Inverse agonist

/

GPR18

/

/

GPR55

/

/

5-HT-1A

/

/

5-HT-2A

/

/

DOR-1

/

/

MOR-1

/

/

Sarizotan

Parkinson’s disease

2;

3

NCT00009048;

NCT00314288;

NCT00105508;

NCT00105521

DRD2

Partial agonist

/

/

DRD3

Ligand

/

5-HT-1A

/

/

Melperone

Parkinson’s disease;

schizophrenia;

anxiety disorders;

depression

2;

3

NCT02374567;

NCT00125138;

DRD2

Antagonist

/

/

Pardoprunox

Parkinson’s disease

3

NCT00407095;

NCT00406588;

NCT00335166;

NCT00335374;

NCT00332917;

NCT00269516

DRD2

/

/

/

DRD3

/

/

DRD4

/

/

5-HT-1A

/

/

Piribedil

Parkinson’s disease

3

NCT01007864

DRD2

/

/

810

DRD3

/

/

Centanafadine

Attention deficit hyperactivity disorder

3

NCT03605849;

NCT03605680;

NCT03605836;

NCT05257265;

NCT05279313;

NCT05428033

/

/

/

 

Raclopride

View full size image

Parkinson’s disease;

depression

1;

4

NCT00832221; NCT05282277

DRD2

Antagonist

/

811

Dipraglurant

Parkinson’s disease

2;

2/3

NCT01336088;

NCT05116813;

NCT04857359

MGLUR5

/

/

/

Arbaclofen Placarbil

Multiple sclerosis

3

NCT01359566

GABBR1

Agonist

/

812

GABBR2

Agonist

/

Plozalizumab

Biotech

Multiple sclerosis

2

NCT01199640

CMKBR2

/

/

/

Nabiximols

Multiple sclerosis

3;

4

NCT01964547;

NCT00678795;

NCT00681538;

NCT00702468;

NCT00711646

GPR12

Inverse agonist

/

658

CB-R

/

/

CB-2

/

/

GPR55

/

/

5-HT-1A

/

/

5-HT-2A

/

/

DOR-1

/

/

MOR-1

/

/

Ceralifimod

Multiple sclerosis

2

NCT01226745

S1PR1

Modulator

/

813

Tiapride

Huntington’s disease;

schizophrenia;

depression;

anxiety disorders

1;

3

NCT00632645;

NCT02374567

DRD2

Blocker

/

814

DRD3

Blocker

/

5-HT

Antagonist

/

ADRA1

Antagonist

/

ADRA2

Antagonist

/

LY2140023

Not Available

Schizophrenia

1;

2;

2/3;

3

NCT01307800;

NCT01328093;

NCT01487083;

NCT01452919;

NCT01129674;

NCT01125358;

NCT01052103;

NCT00149292;

NCT00520923;

NCT00845026; NCT01086748;

NCT01606436;

NCT01354353

MGLUR2

/

/

/

MGLUR3

/

/

BL-1020

Not available

Schizophrenia

2;

2/3

NCT00480571;

NCT00722176

DRD2

/

/

/

5-HT-2A

/

/

Norclozapine

View full size image

Schizophrenia

1;

2

NCT00628420;

NCT00490516

CHRM1

/

/

/

DRD2

/

/

DRD3

/

/

Talnetant

View full size image

Schizophrenia

2

NCT00049946;

NCT00103727;

NCT00300963;

NCT00101985

NK3R

Antagonist

1

815

Blonanserin

Schizophrenia

4;

3

NCT01516424;

NCT03784222

DRD2

Antagonist

/

816

DRD3

Antagonist

/

5-HT-2A

Antagonist

/

Pipamperone

Schizophrenia;

depression;

anxiety disorders

2;

3

NCT00672659; NCT01450514; NCT02374567;

NCT01312922

DRD2

Antagonist

/

/

5-HT-2A

Agonist

/

ADRA1

Antagonist

/

DRD4

Antagonist

/

DRD1

Antagonist

/

DRD3

/

/

5-HT-2B

/

/

ADRA2A

Antagonist

/

Pavinetant

Schizophrenia

2

NCT00686998

NK3R

Antagonist

/

817

Tetrahydrocannabivarin

Schizophrenia

2

NCT01491490

CB-R

Antagonist

/

818

GPR55

Partial agonist

/

5-HT-1A

Agonist

/

CB-2

Partial agonist

/

JNJ-37822681

Schizophrenia

2

NCT00728195;

NCT01812642

DRD2

Antagonist

/

819

SEP-363856

Schizophrenia;

Parkinson’s disease

1;

2;

2/3;

3

NCT04865835;

NCT03370640;

NCT04325737;

NCT04369391;

NCT01940159;

NCT01972711;

NCT01994473;

NCT04038957;

NCT02970929;

NCT02969382;

NCT04825860;

NCT05359081;

NCT04092686;

NCT04072354;

NCT04109950;

NCT02969369

TAAR1

Agonist

/

820

5-HT-1A

Agonist

/

Dimethyltryptamine

Depression

1;

1/2

NCT04711915; NCT04698603

5-HT-6

/

68

821,822

5-HT-2A

/

65

Serotonin

Depression;

bipolar disorder;

anxiety disorders

2;

3;

2/3;

4

NCT02137369; NCT01324700; NCT01811147;

NCT00183274;

NCT00157547;

NCT02356107’

NCT01155661;

NCT00361218

5-HT-2A

/

/

823

5-HT-3A

/

/

5-HT-3B

/

/

5-methoxy-N,N-dimethyltryptamine

Depression

1/2

NCT04698603

5-HT-1A

Agonist

/

824

5-HT-2A

Agonist

/

Tianeptine

Bipolar disorder;

depression

3;

4

NCT00879372;

NCT01309776;

NCT04249596

MOR-1

Agonist

/

440,441

5-HT-1A

Inhibitor

/

DRD3

Agonist

/

Vofopitant

Bipolar disorder

1

NCT00907985

SPR

/

/

825

Naluzotan

Anxiety disorders;

depression

3;

2

NCT00248183;

NCT00448292

5-HT-1A

Agonist

/

435

Ansofaxine

View full size image

Depression

3

NCT04853407

5-HT

/

/

/

Roluperidone

Schizophrenia

3

NCT03397134

5-HT-2A

/

/

402

Eltoprazine

Schizophrenia;

Parkinson’s disease (PD)

2

NCT01266174;

NCT02439125

5-HT-1A

/

/

401

5-HT-2B

/

/

Zicronapine

Schizophrenia

3

NCT01295372

5-HT-2A

/

/

400

5-HT-2C

/

/

DRD1

/

/

DRD2

/

/

Brilaroxazine

Schizophrenia

2;

3

NCT01490086;

NCT05184335

5-HT-7

/

/

399

5-HT-2A

/

/

5-HT-1A

/

/

DRD2

/

/

DRD3

/

/

DRD4

/

/

5-HT-6

/

/

  1. 5-HT 5-hydroxytryptamine receptor, 5-HT-1 5-hydroxytryptamine receptor 1, 5-HT-6 5-hydroxytryptamine receptor 6, 5-HT-1A 5-hydroxytryptamine receptor 1A, 5-HT-1B 5-hydroxytryptamine receptor 1B, 5-HT-1C 5-hydroxytryptamine receptor 1C, 5-HT-1D 5-hydroxytryptamine receptor 1D, 5-HT-1E 5-hydroxytryptamine receptor 1E, 5-HT-1F 5-hydroxytryptamine receptor 1F, 5-HT-2A 5-hydroxytryptamine receptor 2A, 5-HT-2B 5-hydroxytryptamine receptor 2B, 5-HT-2C 5-hydroxytryptamine receptor 2C, 5-HT-3 5-hydroxytryptamine receptor 3A, 5-HT-3A 6-hydroxytryptamine receptor 3A, 5-HT-3B 5-hydroxytryptamine receptor 3B, 5-HT-4 5-hydroxytryptamine receptor 4, 5-HT-7 5-hydroxytryptamine receptor 7, ADRA1 alpha-1 adrenergic receptor, ADRA1A alpha-1A adrenergic receptor, ADRA1B alpha-1B adrenergic receptor, ADRA1D alpha-1D adrenergic receptor, ADRA2 alpha-2 adrenergic receptor, ADRA2A alpha-2A adrenergic receptor, ADRA2B alpha-2B adrenergic receptor, ADRA2C alpha-2C adrenergic receptor, ADRB2 beta-2 adrenergic receptor, ADRB3 beta-3 adrenergic receptor, ADRB1 beta-1 adrenergic receptor, CB-2 cannabinoid receptor 2, CB-R or CB1 cannabinoid receptor 1, CHRM cholinergic receptor muscarinic, CHRM1 muscarinic acetylcholine receptor M1, CHRM2 muscarinic acetylcholine receptor M2, CHRM3 muscarinic acetylcholine receptor M3, CHRM4 muscarinic acetylcholine receptor M4, CHRM5 muscarinic acetylcholine receptor M5, DOR-1 delta-type opioid receptor, DRD1 D(1A) dopamine receptor, DRD2 D(2) dopamine receptor, DRD3 D(3) dopamine receptor, DRD4 D(4) dopamine receptor, DRD5 D(5) dopamine receptor, GABBR1 gamma-aminobutyric acid type B receptor subunit 1, GABBR2 gamma-aminobutyric acid type B receptor subunit 2, GPR18 N-arachidonyl glycine receptor, GPR12 G-protein coupled receptor 12, GPR55 G-protein coupled receptor 55, HH1R histamine H1 receptor, HH2R histamine H2 receptor, HH3R histamine H3 receptor, HH4R histamine H4 receptor, KOR-1 kappa-type opioid receptor, MCHR1 melanin-concentrating hormone receptor 1, MOR-1 mu-type opioid receptor, SPR neurokinin 1 receptor, S1PR1 sphingosine 1-phosphate receptor 1, TAAR1 trace amine-associated receptor 1, Mel-1A-R melatonin receptor type 1A, Mel-1B-R melatonin receptor type 1B, MGLUR5 metabotropic glutamate receptor 5, MGLUR2 metabotropic glutamate receptor 2, MGLUR3 metabotropic glutamate receptor 3, CMKBR2 C-C chemokine receptor type 2, NK3R neuromedin-K receptor
  2. Overview of the clinical stage drugs targeting GPCR for the treatment of neuropsychiatric disorders. The clinical stage compounds and their affiliated items including structure, indication, phase status, NCT number, GPCR targets, mechanism, binding affinity (Ki) and related references were collected from the DrugBank database (Accessed May 2022).
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