DT-Web

DB00235 - Milrinone


Identification
Name Milrinone
Accession Number DB00235 (APRD00010)
Type small molecule
Description A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the ionotropic potency of amrinone. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 211.2194
Groups approved
Monoisotopic Weight 211.074561925
Pharmacology
Indication Indicated for the treatment of congestive heart failure.
Mechanism of action Milrinone inhibits erythrocyte phosphodiesterase, resulting in an increase in erythrocyte cAMP activity. Subsequently, the erythrocyte membrane becomes more resistant to deformity. Along with erythrocyte activity, Milrinone also decreases blood viscosity by reducing plasma fibrinogen concentrations and increasing fibrinolytic activity.
Absorption Milrinone is rapidly and almost completely absorbed after oral administration. Bioavailability is 92% (in healthy volunteers).
Protein binding 70 to 80%
Biotransformation There are five metabolites but the O-glucuronide represents the major pathway of biotransformation.
Route of elimination The primary route of excretion of milrinone in man is via the urine.
Toxicity LD50 = 0.3 mg/L in rats
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


cGMP-inhibited 3',5'-cyclic phosphodiesterase A
Name cGMP-inhibited 3',5'-cyclic phosphodiesterase A
Gene Name PDE3A
Pharmacological action yes
Actions inhibitor
References
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
1971 cAMP-specific 3',5'-cyclic phosphodiesterase 4A PDE4A 0.0601
4200 Cytochrome P450 1A2 CYP1A2 0.054
541 cAMP-specific 3',5'-cyclic phosphodiesterase 4B PDE4B 0.0538
4122 Histone deacetylase 2 HDAC2 0.042
777 Tumor necrosis factor TNF 0.0405
16 Adenosine A1 receptor ADORA1 0.0379
3806 cGMP-dependent 3',5'-cyclic phosphodiesterase PDE2A 0.0302
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.029
4209 ATP-sensitive inward rectifier potassium channel 8 KCNJ8 0.0287
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.027
4512 Cytochrome P450 3A4 CYP3A4 0.0251
4109 cAMP-specific 3',5'-cyclic phosphodiesterase 4C PDE4C 0.0236
695 cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A PDE10A 0.0235
1178 Adenosine A2a receptor ADORA2A 0.022
390 Adenosine A3 receptor ADORA3 0.0206
2358 cAMP-specific 3',5'-cyclic phosphodiesterase 4D PDE4D 0.0195
6143 Solute carrier family 22 member 7 SLC22A7 0.0153
6013 Cytochrome P450 2E1 CYP2E1 0.0123
4119 Cytochrome P450 2D6 CYP2D6 0.0103
6107 Cytochrome P450 3A7 CYP3A7 0.0087
4118 Cytochrome P450 3A5 CYP3A5 0.0083
268 Adenosine A2b receptor ADORA2B 0.008
6016 Cytochrome P450 2C19 CYP2C19 0.0079
204 cGMP-specific 3',5'-cyclic phosphodiesterase PDE5A 0.0058
3957 Adenosine deaminase ADA 0.0053
1898 Cytochrome P450 1B1 CYP1B1 0.0045
6024 Cytochrome P450 1A1 CYP1A1 0.0037
4924 Cytochrome P450 2C8 CYP2C8 0.0032
4757 Cytochrome P450 2C9 CYP2C9 0.0029
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