Identification

Summary

Milrinone is a PDE-III inhibitor with inotropic, lusitropic, and vasodilatory properties used for the short-term treatment of acute decompensated heart failure.

Generic Name
Milrinone
DrugBank Accession Number
DB00235
Background

Heart failure is a multifactorial condition that affects roughly 1-2% of the adult population. Often the result of long-term myocardial ischemia, cardiomyopathy, or other cardiac insults, heart failure results from an inability of the heart to perfuse peripheral tissues with sufficient oxygen and metabolites, resulting in complex systemic pathologies. Heart failure is underpinned by numerous physiological changes, including alteration in β-adrenergic signalling and cyclic adenosine monophosphate (cAMP) production, which affects the heart's contractile function and cardiac output.1 Milrinone is a second-generation bipyridine phosphodiesterase (PDE) inhibitor created through chemical modification of amrinone.2 As a PDE-III inhibitor, milrinone results in increased cAMP levels and improves cardiac function and peripheral vasodilation in acute decongested heart failure.3,7,1,2,4,8

Milrinone was originally synthesized at the Sterling Winthrop Research Institute in the 1980s.2 It was approved by the FDA on December 31, 1987, and was marketed under the trademark PRIMACOR® by Sanofi-Aventis US before being discontinued.8

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 211.2194
Monoisotopic: 211.074561925
Chemical Formula
C12H9N3O
Synonyms
  • 1,6-Dihydro-2-methyl-6-oxo(3,4'-bipyridine)-5-carbonitrile
  • Milrinona
  • Milrinone
  • Milrinonum
External IDs
  • WIN 47,203-2

Pharmacology

Indication

Milrinone is indicated for the short-term (48 hours or less) treatment of patients with acute decompensated heart failure. Milrinone administration should occur together with close monitoring using appropriate electrocardiographic equipment and should occur in a facility equipped for the immediate treatment of potential cardiac events, including ventricular arrhythmias.8

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Milrinone is a bipyridine derivative with positive inotropic and lusitropic effects that also results in peripheral vasodilation with minimal chronotropic effects over a therapeutic range of 100 to 300 ng/mL.8,6 As such, milrinone is used in decompensated congestive heart failure.8 Studies have demonstrated that milrinone exhibits sigmoidal effects, such that increasing milrinone plasma concentrations beyond a certain level results in no further hemodynamic changes.6 Despite milrinone's benefits, both intravenous and oral use has been associated with increased frequency of ventricular arrhythmias, and long-term oral use has been associated with an increased risk of sudden death; in general, there are no data to support the safety or efficacy of milrinone use beyond 48 hours and patients should be monitored closely for cardiac dysfunction.8 Also, as milrinone is primarily excreted renally, dose adjustments may be required in patients with impaired renal function.8

Mechanism of action

Heart failure is a condition characterized by the heart's inability to provide adequate perfusion to the peripheral tissues, resulting in systemic symptoms including pulmonary, gastrointestinal, renal, and cerebral dysfunction.1 Although the biochemical and physiological processes underlying heart failure complex and variable, one such physiological response regulated by the sympathetic nervous system involves the eventual downregulation of cardiac β-receptors, decreased catecholamine sensitivity, and a corresponding decrease in adenylyl-cyclase-mediated signalling pathways.1 Increased intracellular cAMP, mainly acting through protein kinase A, increases sarcolemmal calcium release through L-type calcium channels as well as calcium re-uptake mediated by phospholamban and troponin I; these actions correspond to positive inotropic and lusitropic effects, respectively.1,2

Milrinone is a partial competitive inhibitor of phosphodiesterase III (PDE-III), with a measured IC50 value of between 0.66 and 1.3 μM.3,7 As a PDE-III inhibitor, milrinone results in an increase in intracellular cAMP, responsible for its pharmacological effects, including positive inotropy, positive lusitropy, and vasodilation.1,2,4 As milrinone affects cAMP levels through PDE-III and not through β-adrenergic receptors, it is effective in patients who have downregulated or otherwise desensitized β-adrenergic receptors and can be administered together with β-agonists/antagonists.5,6

TargetActionsOrganism
AcGMP-inhibited 3',5'-cyclic phosphodiesterase A
inhibitor
Humans
Absorption

When administered as an IV bolus dose of 10-100 μg/kg, milrinone induces hemodynamic effects within 60 seconds reaching a peak effect by 2-5 minutes.2 The plasma AUC is significantly dose-dependent.8

Volume of distribution

Milrinone administered intravenously to congestive heart failure patients had a volume of distribution of 0.38 L/kg (injections between 12.5-125 μg/kg) and 0.45 L/kg (infusions between 0.2-0.7 μg/kg/min.8

Protein binding

Milrinone is approximately 70% bound to human plasma proteins.8

Metabolism

Animal studies suggest that two oxidative pathways are involved in milrinone metabolism, albeit only involving a small proportion of the administered dose. The major metabolite is the O-glucuronide metabolite.2,8

Route of elimination

Milrinone is primarily excreted in the urine, with 60% of a dose recovered after two hours and 90% within eight hours. Approximately 83% of milrinone recovered in urine is unchanged while 12% is present as the main O-glucuronide metabolite.2,6,8

Half-life

Milrinone administered intravenously to congestive heart failure patients had a mean terminal elimination half-life of 2.3 hours (injections between 12.5-125 μg/kg) and 2.4 hours (infusions between 0.2-0.7 μg/kg/min.8

Clearance

Milrinone administered intravenously to congestive heart failure patients had a clearance of 0.13 L/kg/hr (injections between 12.5-125 μg/kg) and 0.14 L/kg/hr (infusions between 0.2-0.7 μg/kg/min.8

Adverse Effects
Adverseeffects
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Toxicity

Toxicity information regarding milrinone is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as hypotension and adverse cardiac events such as ventricular arrhythmias. Symptomatic and supportive measures are recommended.8

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirMilrinone may decrease the excretion rate of Abacavir which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Milrinone which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Milrinone which could result in a higher serum level.
AcetaminophenMilrinone may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Milrinone which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Milrinone which could result in a higher serum level.
AclidiniumMilrinone may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineMilrinone may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Milrinone which could result in a higher serum level.
Adefovir dipivoxilAdefovir dipivoxil may decrease the excretion rate of Milrinone which could result in a higher serum level.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Milrinone lactate9K8XR81MO8100286-97-3VWUPWEAFIOQCGF-UHFFFAOYSA-N
International/Other Brands
Corotrop / Corotrope / Milrila
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Milrinone InjectionSolution1 mg / mLIntravenousTEVA Canada Limited2003-05-252015-07-22Canada flag
Milrinone LactateInjection, solution1 mg/1mLIntravenousHospira, Inc.2006-07-172006-07-17US flag
Milrinone Lactate in DextroseInjection200 ug/1mLIntravenousBaxter Healthcare Corporation2006-07-272006-07-27US flag
Milrinone Lactate InjectionSolution1 mg / mLIntravenousSterimax IncNot applicableNot applicableCanada flag
Milrinone Lactate InjectionSolution1 mg / mLIntravenousAuro Pharma Inc2018-12-24Not applicableCanada flag
Milrinone Lactate InjectionSolution1 mg / mLIntravenousStrides Pharma Canada IncNot applicableNot applicableCanada flag
Milrinone Lactate InjectionSolution1 mg / mLIntravenousSandoz Canada Incorporated2003-06-25Not applicableCanada flag
Milrinone Lactate Injection USPSolution1 mg / mLIntravenousMarcan Pharmaceuticals IncNot applicableNot applicableCanada flag
Milrinone Lactate Injection, USPSolution1 mg / mLIntravenousFresenius Kabi2003-07-03Not applicableCanada flag
PrimacorInjection, solution200 ug/1mLIntravenoussanofi-aventis U.S. LLC1987-12-312009-09-30US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-milrinone InjectableSolution1.0 mg / mLIntravenousApotex Corporation2005-07-292013-08-02Canada flag
Milrinone LactateInjection, solution0.2 mg/1mLIntravenousAuroMedics Pharma LLC2020-09-03Not applicableUS flag
Milrinone LactateInjection, solution200 ug/1mLIntravenousHikma Farmaceutica2010-01-212010-01-21US flag
Milrinone LactateInjection, solution1 mg/1mLIntravenousCaplin Steriles Limited2021-04-26Not applicableUS flag
Milrinone LactateInjection1 mg/1mLIntravenousBedford Pharmaceuticals2002-05-272012-05-31US flag
Milrinone LactateInjection, solution1 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2003-10-022008-07-31US flag
Milrinone LactateInjection1 mg/1mLIntravenousGland Pharma Limited2017-07-28Not applicableUS flag
Milrinone LactateInjection, solution200 ug/1mLIntravenousHospira, Inc.2005-06-24Not applicableUS flag
Milrinone LactateInjection, solution1 mg/1mLIntravenousWest-Ward Pharmaceuticals Corp2010-12-03Not applicableUS flag
Milrinone lactateInjection, solution1 mg/1mLIntravenousApotex Corporation2004-09-212010-07-01US flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Milrinone Lactate in DextroseMilrinone lactate (200 ug/1mL) + D-glucose monohydrate (49.4 mg/1mL)InjectionIntravenousB. Braun Medical Inc.2007-10-29Not applicableUS flag

Categories

ATC Codes
C01CE02 — Milrinone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as bipyridines and oligopyridines. These are organic compounds containing two pyridine rings linked to each other.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Bipyridines and oligopyridines
Direct Parent
Bipyridines and oligopyridines
Alternative Parents
3-pyridinecarbonitriles / Methylpyridines / Hydroxypyridines / Heteroaromatic compounds / Nitriles / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Hydrocarbon derivatives
Substituents
3-pyridinecarbonitrile / Aromatic heteromonocyclic compound / Azacycle / Bipyridine / Carbonitrile / Heteroaromatic compound / Hydrocarbon derivative / Hydroxypyridine / Methylpyridine / Nitrile
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
nitrile, pyridone, bipyridines (CHEBI:50693)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
JU9YAX04C7
CAS number
78415-72-2
InChI Key
PZRHRDRVRGEVNW-UHFFFAOYSA-N
InChI
InChI=1S/C12H9N3O/c1-8-11(9-2-4-14-5-3-9)6-10(7-13)12(16)15-8/h2-6H,1H3,(H,15,16)
IUPAC Name
6-methyl-2-oxo-5-(pyridin-4-yl)-1,2-dihydropyridine-3-carbonitrile
SMILES
CC1=C(C=C(C#N)C(=O)N1)C1=CC=NC=C1

References

Synthesis Reference

Baldev Singh, "Preparation of 1,2-dihydro-6-(lower alkyl)-2-oxo-5-(pyridinyl)nicotinonitriles." U.S. Patent US4413127A, issued November 1, 1983.

General References
  1. Tanai E, Frantz S: Pathophysiology of Heart Failure. Compr Physiol. 2015 Dec 15;6(1):187-214. doi: 10.1002/cphy.c140055. [Article]
  2. Shipley JB, Tolman D, Hastillo A, Hess ML: Milrinone: basic and clinical pharmacology and acute and chronic management. Am J Med Sci. 1996 Jun;311(6):286-91. doi: 10.1097/00000441-199606000-00011. [Article]
  3. Kariya T, Wille LJ, Dage RC: Biochemical studies on the mechanism of cardiotonic activity of MDL 17,043. J Cardiovasc Pharmacol. 1982 May-Jun;4(3):509-14. doi: 10.1097/00005344-198205000-00024. [Article]
  4. Colucci WS: Myocardial and vascular actions of milrinone. Eur Heart J. 1989 Aug;10 Suppl C:32-8. doi: 10.1093/eurheartj/10.suppl_c.32. [Article]
  5. Kislitsina ON, Rich JD, Wilcox JE, Pham DT, Churyla A, Vorovich EB, Ghafourian K, Yancy CW: Shock - Classification and Pathophysiological Principles of Therapeutics. Curr Cardiol Rev. 2019;15(2):102-113. doi: 10.2174/1573403X15666181212125024. [Article]
  6. Chong LYZ, Satya K, Kim B, Berkowitz R: Milrinone Dosing and a Culture of Caution in Clinical Practice. Cardiol Rev. 2018 Jan/Feb;26(1):35-42. doi: 10.1097/CRD.0000000000000165. [Article]
  7. Zhang W, Ke H, Colman RW: Identification of interaction sites of cyclic nucleotide phosphodiesterase type 3A with milrinone and cilostazol using molecular modeling and site-directed mutagenesis. Mol Pharmacol. 2002 Sep;62(3):514-20. [Article]
  8. FDA Approved Drug Products: PRIMACOR (milrinone) injection [Link]
  9. MSDS: milrinone [Link]
Human Metabolome Database
HMDB0014380
KEGG Drug
D00417
KEGG Compound
C07224
PubChem Compound
4197
PubChem Substance
46507838
ChemSpider
4052
BindingDB
15296
RxNav
52769
ChEBI
50693
ChEMBL
CHEMBL189
ZINC
ZINC000009224016
Therapeutic Targets Database
DAP000150
PharmGKB
PA164749171
PDBe Ligand
MIL
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Milrinone
PDB Entries
1tlm
FDA label
Download (491 KB)
MSDS
Download (34.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAcute Coronary Syndrome (ACS) / Low Cardiac Output Syndrome / Pulmonary Edemas / Shock, Cardiogenic1
4RecruitingSupportive CarePulmonary Hypertension Due to Left Heart Disease1
4RecruitingTreatmentHemodynamics1
4Unknown StatusTreatmentCardiomyopathy / Septic Shock1
3CompletedTreatmentMitral Valve Insufficiency / Pulmonary Hypertension (PH)1
3CompletedTreatmentOutput, Low Cardiac1
3RecruitingTreatmentCardiac Surgical Procedures (D006348) / Infants / Low Cardiac Output Syndrome1
3RecruitingTreatmentVasospasm1
2CompletedPreventionHeart Defects,Congenital1
2CompletedPreventionPulmonary Hypertension (PH)1

Pharmacoeconomics

Manufacturers
  • App pharmaceuticals llc
  • Baxter healthcare corp anesthesia and critical care
  • Baxter healthcare corp anesthesia critical care
  • Bedford laboratories div ben venue laboratories inc
  • Bioniche pharma usa llc
  • Claris lifesciences ltd
  • Gland pharma ltd
  • Hospira inc
  • International medicated systems ltd
  • B braun medical inc
  • Baxter healthcare corp
  • Bedford laboratories
  • Hikma farmaceutica (portugal) sa
  • Sanofi aventis us llc
Packagers
  • Alchymars SPA
  • Apotex Inc.
  • APP Pharmaceuticals
  • B. Braun Melsungen AG
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bioniche Pharma
  • Cardinal Health
  • Hospira Inc.
  • Sanofi-Aventis Inc.
  • Teva Pharmaceutical Industries Ltd.
Dosage Forms
FormRouteStrength
SolutionIntravenous1.0 mg / mL
Injection, solution, concentrateIntravenous
Injection, solutionParenteral
InjectionIntravenous
SolutionIntravenous
Injection, solutionIntravenous
SolutionIntravenous20 mg
SolutionIntravenous0.01 g
SolutionIntravenous1 mg
SolutionIntravenous22.5 mg/150ml
InjectionIntravenous1 mg/1mL
InjectionIntravenous20 mg/100mL
Injection, solutionIntravenous200 ug/1mL
InjectionIntravenous
InjectionIntravenous200 ug/1mL
Injection, solutionIntravenous0.2 mg/1mL
SolutionIntravenous1 mg / mL
Injection, solution, concentrateIntravenous1 mg/mL
TabletOral10 mg
SolutionIntravenous10 mg
Injection, solutionIntravenous1 mg/1mL
SolutionIntravenous1 mg/1ml
InjectionIntravenous1 mg
Prices
Unit descriptionCostUnit
Primacor 0.2 mg/ml-d5w 100 ml1.6USD ml
Milrinone-d5w 20 mg/100 ml1.45USD ml
Milrinone lact 20 mg/20 ml vial1.44USD ml
Milrinone lact 10 mg/10 ml vial1.31USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)>300 °CChemSpider
water solubility<1 mg/mLChemSpider
Predicted Properties
PropertyValueSource
Water Solubility0.209 mg/mLALOGPS
logP1.04ALOGPS
logP0.33ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)7.54ChemAxon
pKa (Strongest Basic)4.82ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area65.78 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity61.14 m3·mol-1ChemAxon
Polarizability21.46 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9807
Caco-2 permeable+0.6889
P-glycoprotein substrateNon-substrate0.8041
P-glycoprotein inhibitor INon-inhibitor0.7835
P-glycoprotein inhibitor IINon-inhibitor0.9799
Renal organic cation transporterNon-inhibitor0.8614
CYP450 2C9 substrateNon-substrate0.7016
CYP450 2D6 substrateNon-substrate0.8411
CYP450 3A4 substrateNon-substrate0.5641
CYP450 1A2 substrateInhibitor0.5399
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9816
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8827
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7866
Ames testNon AMES toxic0.7822
CarcinogenicityNon-carcinogens0.9351
BiodegradationNot ready biodegradable0.993
Rat acute toxicity2.5820 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.991
hERG inhibition (predictor II)Non-inhibitor0.8941
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03di-0090000000-1894d0a48fc2ccb74718
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03di-0190000000-6ae34a9fd604b709bcc9
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03di-0970000000-c1a7f68e4f0eb27d6881
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-014i-1900000000-8e2c336e4e2425cca486
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-014i-3900000000-047756d13498358fc54d
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-01ta-1910000000-c2df049a2cac6a6ad313
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03dj-3910000000-21cb0ac7a539590cf3a5
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-08n9-7900000000-f774999fc6fb39238858
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00o1-9300000000-9b1eed78c20489183326
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-004l-9100000000-c84b782dfa6c28c15ddc
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-001i-0900000000-969f8d74389284d0c167
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-0790000000-fe6863cad241275fc104

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Milrinone has a measured IC50 value of between 0.66 and 1.3 μM.
General Function
Metal ion binding
Specific Function
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
Gene Name
PDE3A
Uniprot ID
Q14432
Uniprot Name
cGMP-inhibited 3',5'-cyclic phosphodiesterase A
Molecular Weight
124978.06 Da
References
  1. Cone J, Wang S, Tandon N, Fong M, Sun B, Sakurai K, Yoshitake M, Kambayashi J, Liu Y: Comparison of the effects of cilostazol and milrinone on intracellular cAMP levels and cellular function in platelets and cardiac cells. J Cardiovasc Pharmacol. 1999 Oct;34(4):497-504. [Article]
  2. Kuthe A, Magert H, Uckert S, Forssmann WG, Stief CG, Jonas U: Gene expression of the phosphodiesterases 3A and 5A in human corpus cavernosum penis. Eur Urol. 2000 Jul;38(1):108-14. [Article]
  3. Lefievre L, de Lamirande E, Gagnon C: Presence of cyclic nucleotide phosphodiesterases PDE1A, existing as a stable complex with calmodulin, and PDE3A in human spermatozoa. Biol Reprod. 2002 Aug;67(2):423-30. [Article]
  4. Zhang W, Ke H, Colman RW: Identification of interaction sites of cyclic nucleotide phosphodiesterase type 3A with milrinone and cilostazol using molecular modeling and site-directed mutagenesis. Mol Pharmacol. 2002 Sep;62(3):514-20. [Article]
  5. Shakur Y, Fong M, Hensley J, Cone J, Movsesian MA, Kambayashi J, Yoshitake M, Liu Y: Comparison of the effects of cilostazol and milrinone on cAMP-PDE activity, intracellular cAMP and calcium in the heart. Cardiovasc Drugs Ther. 2002 Sep;16(5):417-27. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  7. Kariya T, Wille LJ, Dage RC: Biochemical studies on the mechanism of cardiotonic activity of MDL 17,043. J Cardiovasc Pharmacol. 1982 May-Jun;4(3):509-14. doi: 10.1097/00005344-198205000-00024. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 28, 2021 11:56