Milrinone

Summary

Milrinone (CHEMBL189) is an approved small-molecule platelet aggregation inhibitor (ATC C01CE02) targeting PDE2A, PDE3A, and PDE3B; indicated across 10 conditions including cardiovascular disorder and heart failure.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01CE02
• Targets: 4 (PDE2A, PDE3A, PDE3B…)
• Indications: 10 conditions
• Clinical trials: 41
• Chemistry: 211.22 Da · C12H9N3O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL189
Name	Milrinone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4197
ChEBI	CHEBI:50693
ATC	C01CE02
Molecular formula	C12H9N3O
Molecular weight	211.22
InChIKey	PZRHRDRVRGEVNW-UHFFFAOYSA-N

SMILES: CC1=C(C=C(C(=O)N1)C#N)C2=CC=NC=C2

IUPAC name: 6-methyl-2-oxo-5-pyridin-4-yl-1H-pyridine-3-carbonitrile

ChEBI definition: A member of the class of bipyridines that is 2-pyridone which is substituted at positions 3, 5, and 6 by cyano, pyrid-4-yl, and methyl groups, respectively. It is used (particularly intravenously, as the lactate) for the short-term management of severe heart failure.

Pharmacological roles (ChEBI): platelet aggregation inhibitor, vasodilator agent, cardiotonic drug, EC 3.1.4.17 (3’,5’-cyclic-nucleotide phosphodiesterase) inhibitor.

Also known as: Milrila, Milrinona, Milrinone, NSC-760072, milrinone, SID11111460, SID11111461, SID11114110, SID11532967, SID50104873, SID90341667, SID26757809

Parent form; salt/anhydrous children: CHEMBL1200977

Patent coverage: 5,623 distinct patent families (20,605 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 20,604 (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
PDE2A	phosphodiesterase 2A	Inhibition	6.52	0.3%	O00408
PDE3A	phosphodiesterase 3A	Inhibition	6.36	0.1%	Q14432
PDE3B	phosphodiesterase 3B	Inhibition	6	0.2%	Q13370
PDE5A	phosphodiesterase 5A	Inhibition	7.31	0%	O76074

Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: Lysine-specific demethylase 4E, Prelamin-A/C, RecQ-like DNA helicase BLM, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], cGMP-specific 3’,5’-cyclic phosphodiesterase, Thyrotropin receptor, Beta-lactamase, Phosphodiesterase 4, Phosphodiesterase 3, Phosphodiesterase; PDE3 & PDE4.

Bioactivity

ChEMBL activities: 47 potent at pChembl ≥ 5 of 54 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BLM	7.65	Potency	22.4	nM	CHEMBL_ACT_4741975
BLM	7.65	Potency	22.4	nM	CHEMBL_ACT_4913855
PDE3B	6.82	Ki	150	nM	CHEMBL_ACT_1506639
PDE3B	6.68	IC50	210	nM	CHEMBL_ACT_1883870
PDE3A	6.6	IC50	250	nM	CHEMBL_ACT_22905754
PDE3B	6.55	IC50	280	nM	CHEMBL_ACT_925255
PDE3B	6.52	IC50	300	nM	CHEMBL_ACT_661915
PDE3B	6.44	IC50	360	nM	CHEMBL_ACT_1136476
PDE3B	6.44	IC50	360	nM	CHEMBL_ACT_867101
PDE3A	6.37	AC50	427.9	nM	CHEMBL_ACT_25191112
PDE3A	6.36	IC50	440	nM	CHEMBL_ACT_925256
PDE3B	6.35	IC50	450	nM	CHEMBL_ACT_25084332
PDE3B	6.22	IC50	600	nM	CHEMBL_ACT_1006786
P00811	6.2	Potency	631	nM	CHEMBL_ACT_4636696
PDE3A	6.18	AC50	659.9	nM	CHEMBL_ACT_25192140
PDE3B	6.14	IC50	730	nM	CHEMBL_ACT_112453
PDE3B	6.14	IC50	730	nM	CHEMBL_ACT_1212601
PDE5A	6.13	IC50	740	nM	CHEMBL_ACT_513807
PDE3B	6.07	IC50	860	nM	CHEMBL_ACT_394575
PDE3B	6.07	IC50	860	nM	CHEMBL_ACT_926465
PDE4A	5.96	IC50	1100	nM	CHEMBL_ACT_171621
PDE3B	5.96	IC50	1100	nM	CHEMBL_ACT_920806
PDE3B	5.96	IC50	1100	nM	CHEMBL_ACT_981879
PDE3B	5.82	IC50	1500	nM	CHEMBL_ACT_474145
PDE3B	5.6	IC50	2500	nM	CHEMBL_ACT_1004264
PDE3B	5.6	IC50	2500	nM	CHEMBL_ACT_1219487
PDE3B	5.6	IC50	2500	nM	CHEMBL_ACT_40344
PDE3B	5.6	IC50	2500	nM	CHEMBL_ACT_860566
PDE3B	5.52	IC50	3000	nM	CHEMBL_ACT_957660
PDE3B	5.48	IC50	3300	nM	CHEMBL_ACT_10987565

Target pathways

Aggregated over 4 target gene(s): PDE2A, PDE3A, PDE3B, PDE5A.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
G alpha (s) signalling events	3	PDE2A, PDE3A, PDE3B
cGMP effects	2	PDE2A, PDE5A
PDE3B signalling	1	PDE3B
Smooth Muscle Contraction	1	PDE5A
RHOBTB1 GTPase cycle	1	PDE5A

Dominant GO biological processes

GO term	Targets
negative regulation of cAMP/PKA signal transduction	4
signal transduction	4
negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	3
obsolete cGMP-mediated signaling	2
negative regulation of vascular permeability	2
positive regulation of vascular permeability	2
cGMP catabolic process	2
cellular response to cGMP	2
cellular response to transforming growth factor beta stimulus	2
G protein-coupled receptor signaling pathway	2
negative regulation of transcription by RNA polymerase II	1
heart valve development	1
ventricular septum development	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
positive regulation of gene expression	1

Indications & clinical

Indications

10 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
heart failure	3	MONDO:0005252	EFO:0003144
congenital heart disease	2	MONDO:0005453	EFO:0005207
intracranial vasospasm	2	MONDO:0006812	EFO:1000994
subarachnoid hemorrhage	2	MONDO:0005099	EFO:0000713
pulmonary hypertension	2	MONDO:0005149	MONDO:0005149
toxic shock syndrome	2	MONDO:0001881	EFO:0006834
ischemia reperfusion injury	1	MONDO:0005203	EFO:0002687

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

Clinical trials

Total trials: 41.

Phase distribution

Phase	Trials
PHASE2	13
Not specified	10
PHASE4	6
PHASE3	5
PHASE1/PHASE2	4
PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04484675	PHASE4	RECRUITING	Inhaled and Intravenous Milrinone in Patients With Severe Pulmonary Hypertension
NCT05267886	PHASE4	RECRUITING	CAPITAL DOREMI 2: Inotrope Versus Placebo Therapy for Cardiogenic Shock
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03207165	PHASE4	COMPLETED	Milrinone Versus Dobutamine in Critically Ill Patients
NCT03855579	PHASE4	UNKNOWN	Levosimendan Versus Milrinone in Off Pump CABG Surgery
NCT05132153	PHASE4	UNKNOWN	Effect of Nebulized Milrinone on Right Ventricular Hemodynamics in Adult Cardiac Surgery
NCT06679855	PHASE3	RECRUITING	Milrinone for Prevention of Post-ligation Cardiac Syndrome Trial
NCT00446017	PHASE3	COMPLETED	The Effects of Adrenaline and Milrinone in Patients With Myocardial Dysfunction After CABG
NCT01621971	PHASE3	COMPLETED	Effect of Brief Nebulization of Milrinone on Pulmonary Arterial Pressure Before Cardiopulmonary Bypass on Mitral Valve Surgery Patients
NCT03823781	PHASE3	UNKNOWN	Prophylactic Use of Milrinone After Congenital Heart Surgery in Infants
NCT04362527	PHASE3	COMPLETED	Milrinone Infusion for VAsospam Treatment in Subarachnoid hemoRrhage
NCT05838846	PHASE2/PHASE3	COMPLETED	Inhaled Versus Intravenous Milrinone for Patients Undergoing Mitral Valve Replacement Surgery
NCT04282629	PHASE2	RECRUITING	Cerebral Hemodynamic Optimization by Milrinone to Prevent Delayed Cerebral Ischemia
NCT05450328	PHASE2	NOT_YET_RECRUITING	Inhaled Milrinone and Epoprostenol for the Prevention of Difficult Cardiac Pulmonary Bypass Separation
NCT00543309	PHASE2	TERMINATED	Effects of Perioperative Nesiritide or Milrinone Infusion on Recovery From Fontan Surgery
NCT00549107	PHASE2	UNKNOWN	Prophylactic Use of Levosimendan Versus Milrinone in Open Heart Surgery in Infants
NCT00819377	PHASE2	COMPLETED	Milrinone Inhaled in Cardiac Surgery
NCT01576094	PHASE1/PHASE2	COMPLETED	Two Inodilators Postsurgery in Neonates
NCT01841177	PHASE2	COMPLETED	Evaluating Precision of Therapy - Milrinone
NCT01849094	PHASE1/PHASE2	COMPLETED	Evaluating the Safety, Pharmacokinetics and Haemodynamic Effect of a Slow Release Oral Formulation of Milrinone
NCT01956006	PHASE1/PHASE2	COMPLETED	Pilot Study of Slow Release Oral Milrinone in Patients With Advanced Heart Failure
NCT02098629	PHASE2	COMPLETED	Concomitant Milrinone and Esmolol Treatment in Patients with Acute Myocardial Infarction
NCT02232399	PHASE2	COMPLETED	Is Levosimendan Superior to Milrinone Regarding Acute Kidney Injury After Cardiac Surgery for Congenital Heart Disease?
NCT02595541	PHASE1/PHASE2	COMPLETED	Oral Sildenafil and Intravenous Milrinone on Postoperative Pulmonary Hypertension
NCT02644057	PHASE2	WITHDRAWN	Dobutamaine Versus Milrinone in Cardiorenal Syndrome
NCT02712788	PHASE2	TERMINATED	Milrinone in Addition to Hyperdynamic Therapy in the Treatment of Vasospasm Following Aneurysmal Subarachnoid Hemorrhage
NCT02951130	PHASE2	COMPLETED	Milrinone in Congenital Diaphragmatic Hernia
NCT05122884	PHASE2	UNKNOWN	Milrinone Versus Placebo in Patients With Septic Shock
NCT05131867	PHASE2	COMPLETED	Management of Cerebral Vascular Spasm in Posttraumatic Subarachnoid Hemorrhage Using Combination Therapy
NCT01571037	PHASE1	COMPLETED	Inhaled Milrinone Use in Patients Receiving HeartMate II LVAD: A Pilot Study
NCT04391478	PHASE1	COMPLETED	Efficacy and Safety of Milrinone Versus Sildenafil in the Treatment of Neonates With Persistent Pulmonary Hypertension
NCT07144267	Not specified	NOT_YET_RECRUITING	Comparison of Milrinone and Epinephrine on TAPSE
NCT00695929	Not specified	COMPLETED	Levosimendan in Congenital Cardiac Surgery
NCT00966745	Not specified	COMPLETED	Milrinone During Living Donor Hepatectomy
NCT02408003	Not specified	COMPLETED	Changes in Cardiac Deformation Following Physiologic Alterations and Inotropic Support.
NCT02549066	Not specified	COMPLETED	Impact of CArdiopulmonary Bypass Flow on Renal Blood Flow, Function and OXygenation
NCT02726620	Not specified	COMPLETED	Decision Support for Intraoperative Low Blood Pressure
NCT04153383	Not specified	UNKNOWN	Milrinone on Cardiac Performance During Off-pump Coronary Artery Bypass Surgery
NCT06077721	Not specified	UNKNOWN	Milrinone on Right Ventricular Strain in Cardiac Surgery
NCT06562036	Not specified	COMPLETED	Efficacy of Milrinone With Sildenafil in Persistent Pulmonary Hypertension in Children

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

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

Molecule	Source	Status	Shared targets
SILDENAFIL	ChEMBL + PubChem	Phase 4 (approved)	PDE2A, PDE3A, PDE3B, PDE5A
Tadalafil	ChEMBL + PubChem	Phase 4 (approved)	PDE2A, PDE3A, PDE3B, PDE5A
VARDENAFIL	ChEMBL + PubChem	Phase 4 (approved)	PDE2A, PDE3A, PDE3B, PDE5A
DIPYRIDAMOLE	ChEMBL	Phase 4 (approved)	PDE2A, PDE3A, PDE3B, PDE5A
PAPAVERINE	ChEMBL	Phase 3	PDE2A, PDE3A, PDE3B, PDE5A
ANAGRELIDE	ChEMBL + PubChem	Phase 4 (approved)	PDE2A, PDE3A, PDE3B
IBUDILAST	ChEMBL	Phase 4 (approved)	PDE3A, PDE3B, PDE5A
CILOSTAMIDE	ChEMBL	Phase 2	PDE3A, PDE3B, PDE5A
ISOMAZOLE	ChEMBL	Phase 2	PDE3A, PDE3B, PDE5A
SULMAZOLE	ChEMBL	Phase 2	PDE3A, PDE3B, PDE5A
CLOFARABINE	ChEMBL + PubChem	Phase 4 (approved)	PDE2A, PDE3A
LOSARTAN	ChEMBL + PubChem	Phase 4 (approved)	PDE3A, PDE3B
CILOSTAZOL	ChEMBL	Phase 4 (approved)	PDE3A, PDE3B
CRISABOROLE	ChEMBL	Phase 4 (approved)	PDE3A, PDE3B
ENOXIMONE	ChEMBL	Phase 4 (approved)	PDE3A, PDE3B
INAMRINONE	ChEMBL	Phase 4 (approved)	PDE3A, PDE3B
LEVOSIMENDAN	ChEMBL	Phase 3	PDE3A, PDE3B
ADIBENDAN	ChEMBL	Phase 2	PDE3A, PDE3B
BEMARINONE	ChEMBL	Phase 2	PDE3A, PDE3B
BEMORADAN	ChEMBL	Phase 2	PDE3A, PDE3B
CC-115	ChEMBL	Phase 2	PDE3A, PDE3B
ETAZOLATE	ChEMBL	Phase 2	PDE3A, PDE3B
IMAZODAN	ChEMBL	Phase 2	PDE3A, PDE3B
INDOLIDAN	ChEMBL	Phase 2	PDE3A, PDE3B
LIXAZINONE	ChEMBL	Phase 2	PDE3A, PDE3B
MEDORINONE	ChEMBL	Phase 2	PDE3A, PDE3B
MERIBENDAN	ChEMBL	Phase 2	PDE3A, PDE3B
ORISMILAST	ChEMBL	Phase 2	PDE3A, PDE3B
OXAGRELATE	ChEMBL	Phase 2	PDE3A, PDE3B
PIMOBENDAN	ChEMBL	Phase 2	PDE3A, PDE3B
PIROXIMONE	ChEMBL	Phase 2	PDE3A, PDE3B
QUAZINONE	ChEMBL	Phase 2	PDE3A, PDE3B
SIMENDAN	ChEMBL	Phase 2	PDE3A, PDE3B
VESNARINONE	ChEMBL	Phase 2	PDE3A, PDE3B
ZAPRINAST	ChEMBL	Phase 2	PDE2A, PDE5A
ZARDAVERINE	ChEMBL	Phase 2	PDE3A, PDE3B
IDELALISIB	ChEMBL + PubChem	Phase 4 (approved)	PDE3A
TAFAMIDIS	ChEMBL + PubChem	Phase 4 (approved)	PDE3A
TAVABOROLE	ChEMBL + PubChem	Phase 4 (approved)	PDE3A
ACARBOSE	ChEMBL	Phase 4 (approved)	PDE3A
ADENOSINE	ChEMBL	Phase 4 (approved)	PDE3A
ALECTINIB	ChEMBL	Phase 4 (approved)	PDE3A
ALENDRONIC ACID	ChEMBL	Phase 4 (approved)	PDE3A
AMINOGLUTETHIMIDE	ChEMBL	Phase 4 (approved)	PDE3A
AMLEXANOX	ChEMBL	Phase 4 (approved)	PDE3A
ANTAZOLINE	ChEMBL	Phase 4 (approved)	PDE3A
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	PDE3A
AVANAFIL	ChEMBL	Phase 4 (approved)	PDE5A
BENAZEPRIL	ChEMBL	Phase 4 (approved)	PDE3A
BENZBROMARONE	ChEMBL	Phase 4 (approved)	PDE3A
BITHIONOL	ChEMBL	Phase 4 (approved)	PDE3A
CABOZANTINIB	ChEMBL	Phase 4 (approved)	PDE3A
CALCITRIOL	ChEMBL	Phase 4 (approved)	PDE3A
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	PDE3A
CANNABIDIOL	ChEMBL	Phase 4 (approved)	PDE3A
CEFOPERAZONE	ChEMBL	Phase 4 (approved)	PDE3A
CELECOXIB	ChEMBL	Phase 4 (approved)	PDE5A
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	PDE3A
CHLOROQUINE	ChEMBL	Phase 4 (approved)	PDE3A
CHOLIC ACID	ChEMBL	Phase 4 (approved)	PDE3A