Pindolol

Summary

Pindolol (CHEMBL500) is an approved small-molecule serotonergic antagonist (ATC C07AA03) targeting HTR1A, ADRB1, and ADRB2; indicated across 4 conditions including cardiovascular disorder and major depressive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C07AA03
• Targets: 6 (HTR1A, ADRB1, ADRB2…)
• Indications: 4 conditions
• Clinical trials: 9
• Chemistry: 248.32 Da · C14H20N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL500
Name	Pindolol
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4828
ChEBI	CHEBI:8214
ATC	C07AA03
Molecular formula	C14H20N2O2
Molecular weight	248.32
InChIKey	JZQKKSLKJUAGIC-UHFFFAOYSA-N

SMILES: CC(C)NCC(COC1=CC=CC2=C1C=CN2)O

IUPAC name: 1-(1H-indol-4-yloxy)-3-(propan-2-ylamino)propan-2-ol

ChEBI definition: A member of the class of indols which is the 2-hydroxy-3-(isopropylamino)propyl ether derivative of 1H-indol-4-ol.

Pharmacological roles (ChEBI): serotonergic antagonist, β-adrenergic antagonist, antihypertensive agent, vasodilator agent, antiglaucoma drug.

Also known as: (+/-)-LB-46, (rs)-pindolol, Apo-pindol, Betadren, Betapindol, Blocklin-l, Calvisken, Carvisken, Decreten, Dl-lb-46, Dl-pindolol, Durapindol

Patent coverage: 7,330 distinct patent families (28,693 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 28,690 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
HTR1A	5-HT1A receptor	Antagonist	8.1	0%	P08908
ADRB1	β1-adrenoceptor	Partial agonist	9.3	0%	P08588
ADRB2	β2-adrenoceptor	Partial agonist	9.4	0.4%	P07550
ADRB3	β3-adrenoceptor	Partial agonist	7.1	0.1%	P13945
HTR2A	5-HT2A receptor	Full agonist	5	0%	P28223
HTR2B	5-HT2B receptor	Full agonist	5.7	0.4%	P41595

Broader ChEMBL bioactivity targets: 26 (assay-derived). Sample: Prelamin-A/C, Endonuclease 4, 5-hydroxytryptamine receptor 1B, Serotonin 2 (5-HT2) receptor, Serotonin 1 (5-HT1) receptor, Beta-2 adrenergic receptor, Beta-1 adrenergic receptor, 5-hydroxytryptamine receptor 1A, D(4) dopamine receptor, 5-hydroxytryptamine receptor 2C.

Bioactivity

ChEMBL activities: 50 potent at pChembl ≥ 5 of 56 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ADRB2	9.49	Ki	0.32	nM	CHEMBL_ACT_25553923
ADRB2	9.42	Ki	0.38	nM	CHEMBL_ACT_7725988
ADRB2	9.4	Ki	0.4	nM	CHEMBL_ACT_1985057
ADRB1	9.28	Ki	0.52	nM	CHEMBL_ACT_1985056
ADRB2	9.27	Kd	0.54	nM	CHEMBL_ACT_6360553
ADRB1	9.27	Ki	0.53	nM	CHEMBL_ACT_7725986
ADRB2	9.26	IC50	0.55	nM	CHEMBL_ACT_7725987
ADRB2	9.18	Kd	0.66	nM	CHEMBL_ACT_6360486
ADRB1	9.04	IC50	0.92	nM	CHEMBL_ACT_7725985
ADRB2	8.66	IC50	2.19	nM	CHEMBL_ACT_25751541
ADRB1	8.62	Kd	2.4	nM	CHEMBL_ACT_6360521
ADRB1	8.58	Kd	2.63	nM	CHEMBL_ACT_6360571
ADRB1	8.4	AC50	4	nM	CHEMBL_ACT_25121438
ADRB2	8.31	Ki	4.91	nM	CHEMBL_ACT_25741567
ADRB2	8.22	AC50	6	nM	CHEMBL_ACT_25122607
P19327	7.7	Ki	20	nM	CHEMBL_ACT_226482
P19327	7.66	Ki	21.88	nM	CHEMBL_ACT_836414
HTR1A	7.65	Ki	22.4	nM	CHEMBL_ACT_1984984
HTR1A	7.62	Ki	24	nM	CHEMBL_ACT_1138400
HTR1A	7.57	EC50	27	nM	CHEMBL_ACT_1138401
P19327	7.57	Ki	27	nM	CHEMBL_ACT_7730210
P08482	7.5	Potency	31.6	nM	CHEMBL_ACT_4803463
P19327	7.32	IC50	48	nM	CHEMBL_ACT_7730209
HTR1A	7.25	AC50	56.8	nM	CHEMBL_ACT_25164396
HTR1A	7.2	Kd	63.1	nM	CHEMBL_ACT_2930069
ADRB3	7.18	Ki	66	nM	CHEMBL_ACT_7725990
P28564	7.1	Ki	80	nM	CHEMBL_ACT_226483
HTR1A	7.09	Ki	81.1	nM	CHEMBL_ACT_1984985
ADRB3	7.06	IC50	88	nM	CHEMBL_ACT_7725989
HTR1A	7.03	AC50	94	nM	CHEMBL_ACT_25215773

Target pathways

Aggregated over 6 target gene(s): HTR1A, ADRB1, ADRB2, ADRB3, HTR2A, HTR2B.

Top Reactome pathways

18 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	6	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
Signaling by GPCR	6	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
Class A/1 (Rhodopsin-like receptors)	6	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
Amine ligand-binding receptors	6	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
GPCR ligand binding	6	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
GPCR downstream signalling	5	ADRB1, ADRB2, ADRB3, HTR2A, HTR2B
Serotonin receptors	3	HTR1A, HTR2A, HTR2B
Adrenoceptors	3	ADRB1, ADRB2, ADRB3
G alpha (s) signalling events	3	ADRB1, ADRB2, ADRB3
G alpha (q) signalling events	2	HTR2A, HTR2B
Membrane Trafficking	1	ADRB2
Metabolism of proteins	1	ADRB2
Vesicle-mediated transport	1	ADRB2
Deubiquitination	1	ADRB2
Ub-specific processing proteases	1	ADRB2
Post-translational protein modification	1	ADRB2
Cargo recognition for clathrin-mediated endocytosis	1	ADRB2
Clathrin-mediated endocytosis	1	ADRB2

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	6
signal transduction	6
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	4
adenylate cyclase-activating G protein-coupled receptor signaling pathway	4
serotonin receptor signaling pathway	3
chemical synaptic transmission	3
positive regulation of cell population proliferation	3
G protein-coupled serotonin receptor signaling pathway	3
diet induced thermogenesis	3
norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure	3
response to cold	3
heat generation	3
negative regulation of multicellular organism growth	3
positive regulation of MAPK cascade	3
brown fat cell differentiation	3

Indications & clinical

Indications

4 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
major depressive disorder	2	MONDO:0002009	MONDO:0002009
depressive disorder	2	MONDO:0002050	MONDO:0002050

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
Not specified	3
PHASE2	2
PHASE1	2
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01219686	PHASE2/PHASE3	TERMINATED	EScitalopram PIndolol ONset of Action
NCT00931775	PHASE2	COMPLETED	Citalopram Versus Citalopram Plus Pindolol in Major Depressive Disorder
NCT01950520	PHASE2	COMPLETED	Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate
NCT00895804	PHASE1	COMPLETED	Pharmacological Interaction Between Pindolol and MDMA (3,4-Methylenedioxymethamphetamine)
NCT01400165	PHASE1	UNKNOWN	Comparison of the Pharmacokinetics of Three Generic Medications and Their Respective Brand Preparations
NCT07565493	EARLY_PHASE1	NOT_YET_RECRUITING	Psilocybin Administration With 5-HT1a Blockade
NCT00159146	Not specified	TERMINATED	Trial of Pindolol Augmentation in Venlafaxine Treated Patients With Major Depression
NCT00424801	Not specified	TERMINATED	Effects of Intensive Long-Term Vasodilation in Hypertensive Patients With Microvascular Angina Pectoris
NCT01778686	Not specified	COMPLETED	Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (2) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for acebutolol, atenolol, betaxolol, biso	CPIC	ADRA2C;ADRB1;GRK4;GRK5
Annotation of CPIC Guideline for carvedilol, labetalol, nadolol, pindo	CPIC	ADRB2

PharmGKB also curates 0 clinical and 2 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

785 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
Fidaxomicin	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
Propoxyphene	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
TEGASEROD	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
CARVEDILOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
PIMOZIDE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
PROPRANOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
SALMETEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
THIORIDAZINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
BOPINDOLOL	ChEMBL	Phase 2	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
Bosentan	PubChem	Approved	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
Linagliptin	PubChem	Approved	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
Pyrazinamide	PubChem	Approved	ADRB1, ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
ALMOTRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
Crizotinib	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR2A, HTR2B
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
OLODATEROL	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
TAMSULOSIN	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
AMLODIPINE	ChEMBL	Phase 4 (approved)	ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB3, HTR1A, HTR2A, HTR2B
BENPERIDOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
CLEMASTINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR2A, HTR2B
DOMPERIDONE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
DOXAZOSIN	ChEMBL	Phase 4 (approved)	ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
EBASTINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB3, HTR1A, HTR2A, HTR2B
ERGOTAMINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
HALOPERIDOL	ChEMBL	Phase 4 (approved)	ADRB2, ADRB3, HTR1A, HTR2A, HTR2B
LABETALOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR1A, HTR2B
NEBIVOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB3, HTR1A, HTR2A, HTR2B
PROPAFENONE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR2A, HTR2B
SUNITINIB	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
TAMOXIFEN	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2, ADRB3, HTR2A, HTR2B
LISURIDE	ChEMBL	Phase 3	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
OTILONIUM BROMIDE	ChEMBL	Phase 3	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
ALPRENOLOL	ChEMBL	Phase 2	ADRB1, ADRB2, ADRB3, HTR1A, HTR2B
AMOSULALOL	ChEMBL	Phase 2	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
BENZETHONIUM	ChEMBL	Phase 2	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
DOMIPHEN	ChEMBL	Phase 2	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
LEVOPROPRANOLOL	ChEMBL	Phase 2	ADRB1, ADRB2, ADRB3, HTR2A, HTR2B
LYSERGIDE	ChEMBL	Phase 2	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
NEMONAPRIDE	ChEMBL	Phase 2	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
NYLIDRIN	ChEMBL	Phase 2	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
SPIRAMIDE	ChEMBL	Phase 2	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
Afatinib	PubChem	Approved	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
Apixaban	PubChem	Approved	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B
Binimetinib	PubChem	Approved	ADRB1, ADRB2, HTR1A, HTR2A, HTR2B