DT-Web

DB01427 - Amrinone


Identification
Name Amrinone
Accession Number DB01427
Type small molecule
Description Amrinone (or inamrinone) is a type 3 pyridine phosphodiesterase inhibitor. It is used in the treatment of congestive heart failure.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 187.198
Groups approved
Monoisotopic Weight 187.074561925
Pharmacology
Indication Used in the treatment of congestive heart failure.
Mechanism of action Amrinone is a phosphodiesterase inhibitor (PDE3), resulting in increased cAMP and cGMP which leads to an increase in the calcium influx like that caused by beta-agonists resulting in increased inotropic effect.
Absorption Not Available
Protein binding 10 to 49%
Biotransformation Hepatic.
Route of elimination The primary route of excretion in man is via the urine as both inamrinone and several metabolites (N-glycolyl, N-acetate, O-glucuronide and N-glucuronide).
Toxicity Not Available
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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Kobayashi T, Sugawara Y, Ohkubo T, Imamura H, Makuuchi M: Effects of amrinone on hepatic ischemia-reperfusion injury in rats. J Hepatol. 2002 Jul;37(1):31-8. - Pubmed
  • Ko Y, Morita K, Nagahori R, Kinouchi K, Shinohara G, Kagawa H, Hashimoto K: Myocardial cyclic AMP augmentation with high-dose PDEIII inhibitor in terminal warm blood cardioplegia. Ann Thorac Cardiovasc Surg. 2009 Oct;15(5):311-7. - Pubmed
  • Kucuk C, Akcan A, Akyyldyz H, Akgun H, Muhtaroglu S, Sozuer E: Effects of amrinone in an experimental model of hepatic ischemia-reperfusion injury. J Surg Res. 2009 Jan;151(1):74-9. Epub 2008 Mar 13. - Pubmed
DTHybrid score Not Available
cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Name cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Gene Name PDE4B
Pharmacological action unknown
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score Not Available
Tumor necrosis factor
Name Tumor necrosis factor
Gene Name TNF
Pharmacological action unknown
Actions inhibitor
References
  • Kumar A, Kosuri R, Kandula P, Dimou C, Allen J, Parrillo JE: Effects of epinephrine and amrinone on contractility and cyclic adenosine monophosphate generation of tumor necrosis factor alpha-exposed cardiac myocytes. Crit Care Med. 1999 Feb;27(2):286-92. - Pubmed
  • Bergman MR, Kao RH, McCune SA, Holycross BJ: Myocardial tumor necrosis factor-alpha secretion in hypertensive and heart failure-prone rats. Am J Physiol. 1999 Aug;277(2 Pt 2):H543-50. - Pubmed
  • Haddad JJ, Land SC, Tarnow-Mordi WO, Zembala M, Kowalczyk D, Lauterbach R: Immunopharmacological potential of selective phosphodiesterase inhibition. I. Differential regulation of lipopolysaccharide-mediated proinflammatory cytokine (interleukin-6 and tumor necrosis factor-alpha) biosynthesis in alveolar epithelial cells. J Pharmacol Exp Ther. 2002 Feb;300(2):559-66. - Pubmed
  • Marx D, Tassabehji M, Heer S, Huttenbrink KB, Szelenyi I: Modulation of TNF and GM-CSF release from dispersed human nasal polyp cells and human whole blood by inhibitors of different PDE isoenzymes and glucocorticoids. Pulm Pharmacol Ther. 2002;15(1):7-15. - Pubmed
  • Giroir BP, Beutler B: Effect of amrinone on tumor necrosis factor production in endotoxic shock. Circ Shock. 1992 Mar;36(3):200-7. - Pubmed
DTHybrid score 0.7119

Predictions


Id Partner name Gene Name Score
2358 cAMP-specific 3',5'-cyclic phosphodiesterase 4D PDE4D 0.2496
1971 cAMP-specific 3',5'-cyclic phosphodiesterase 4A PDE4A 0.1699
4200 Cytochrome P450 1A2 CYP1A2 0.0938
4109 cAMP-specific 3',5'-cyclic phosphodiesterase 4C PDE4C 0.0924
16 Adenosine A1 receptor ADORA1 0.071
1178 Adenosine A2a receptor ADORA2A 0.0558
695 cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A PDE10A 0.0553
4512 Cytochrome P450 3A4 CYP3A4 0.0502
4122 Histone deacetylase 2 HDAC2 0.0454
2684 Histidine triad nucleotide-binding protein 1 HINT1 0.0408
6013 Cytochrome P450 2E1 CYP2E1 0.0391
268 Adenosine A2b receptor ADORA2B 0.0363
6024 Cytochrome P450 1A1 CYP1A1 0.0337
1787 Nuclear factor NF-kappa-B p105 subunit NFKB1 0.0335
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
290 Prostaglandin G/H synthase 2 PTGS2 0.0287
1820 Beta-nerve growth factor NGF 0.0274
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.027
3090 Chitosanase csn 0.0265
4149 Nuclear factor NF-kappa-B p100 subunit NFKB2 0.0265
4118 Cytochrome P450 3A5 CYP3A5 0.0237
1253 Interferon gamma IFNG 0.023
6016 Cytochrome P450 2C19 CYP2C19 0.0227
2782 Complement C1s subcomponent C1S 0.0213
2232 Interleukin-5 IL5 0.0211
1593 Mucin-2 MUC2 0.021
390 Adenosine A3 receptor ADORA3 0.0206
1588 Multidrug resistance protein 1 ABCB1 0.0203
4119 Cytochrome P450 2D6 CYP2D6 0.02
3815 Complement C1q subcomponent subunit A C1QA 0.0197
3816 Complement C1q subcomponent subunit B C1QB 0.0197
3817 Complement C1q subcomponent subunit C C1QC 0.0196
1102 Low affinity immunoglobulin gamma Fc region receptor III-B FCGR3B 0.0194
3818 Low affinity immunoglobulin gamma Fc region receptor III-A FCGR3A 0.0194
3814 Complement C1r subcomponent C1R 0.0194
3819 Low affinity immunoglobulin gamma Fc region receptor II-a FCGR2A 0.0194
3821 Low affinity immunoglobulin gamma Fc region receptor II-c FCGR2C 0.0194
3820 Low affinity immunoglobulin gamma Fc region receptor II-b FCGR2B 0.0192
784 High affinity immunoglobulin gamma Fc receptor I FCGR1A 0.0186
2112 Toll-like receptor 9 TLR9 0.0185
4757 Cytochrome P450 2C9 CYP2C9 0.0184
6143 Solute carrier family 22 member 7 SLC22A7 0.0175
1517 Beta-3 adrenergic receptor ADRB3 0.0172
65 Matrix metalloproteinase-9 Not Available 0.0171
204 cGMP-specific 3',5'-cyclic phosphodiesterase PDE5A 0.017
1123 Eosinophil cationic protein RNASE3 0.0168
691 cAMP-specific 3',5'-cyclic phosphodiesterase 7B PDE7B 0.0164
779 High-affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A PDE7A 0.0162
1789 Lymphotoxin-alpha LTA 0.0156
1269 Tumor necrosis factor receptor superfamily member 1B TNFRSF1B 0.0156
778 Cysteinyl leukotriene receptor 1 CYSLTR1 0.0149
4924 Cytochrome P450 2C8 CYP2C8 0.0141
3932 Glutathione S-transferase A2 GSTA2 0.0138
193 Beta-1 adrenergic receptor ADRB1 0.0126
823 Fibroblast growth factor receptor 2 FGFR2 0.0126
766 Beta-2 adrenergic receptor ADRB2 0.0124
6107 Cytochrome P450 3A7 CYP3A7 0.0108
1830 5'-nucleotidase NT5E 0.0104
1898 Cytochrome P450 1B1 CYP1B1 0.0094
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0086
6216 High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A PDE8A 0.0083
3957 Adenosine deaminase ADA 0.0083
6217 High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B PDE8B 0.0081
2347 Proto-oncogene serine/threonine-protein kinase Pim-1 PIM1 0.007
20 Prostaglandin G/H synthase 1 PTGS1 0.0068
5691 DTDP-4-DEHYDRORHAMNOSE 3,5-EPIMERASE RMLC rmlC 0.0067
3361 Serpin B5 SERPINB5 0.0067
5694 Transcription antiterminator licT licT 0.0067
1792 Tissue-type plasminogen activator PLAT 0.0066
527 Prostacyclin receptor PTGIR 0.006
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.0055
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0054
56 Delta-aminolevulinic acid dehydratase ALAD 0.0054
2356 Delta-aminolevulinic acid dehydratase hemB 0.0054
3613 Delta-aminolevulinic acid dehydratase hemB 0.0054
3674 Delta-aminolevulinic acid dehydratase hemB 0.0054
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0053
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0052
2286 Isocitrate dehydrogenase [NADP] icd 0.0051
2302 Isocitrate dehydrogenase [NADP] icd 0.0051
2771 Isocitrate dehydrogenase [NADP] icd 0.0051
851 5'-AMP-activated protein kinase subunit beta-2 PRKAB2 0.0049
388 AMP deaminase 1 AMPD1 0.0049
4534 Cytohesin-2 CYTH2 0.0048
814 Ryanodine receptor 1 RYR1 0.0048
3668 Maltose-binding periplasmic protein precursor malE 0.0047
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0043
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0042
1291 cAMP response element-binding protein CREB1 0.0042
386 Acetyl-coenzyme A synthetase, cytoplasmic ACSS2 0.0042
821 Acetyl-coenzyme A synthetase 2-like, mitochondrial ACSS1 0.0042
704 Long-chain-fatty-acid--CoA ligase 1 ACSL1 0.0042
297 Adenylate cyclase type 1 ADCY1 0.0042
2592 Beta-galactosidase lacZ 0.0042
281 5'-AMP-activated protein kinase subunit beta-1 PRKAB1 0.004
315 Arginase-1 ARG1 0.004
748 5'-AMP-activated protein kinase catalytic subunit alpha-1 PRKAA1 0.0039
128 Adenine phosphoribosyltransferase APRT 0.0038
4198 Fructose-1,6-bisphosphatase 1 FBP1 0.0038
6021 Adenosine kinase ADK 0.0037
492 Histamine H1 receptor HRH1 0.0035
10 Glycogen phosphorylase, liver form PYGL 0.0035
24 Thymidylate synthase TMP1 0.0033
359 Thymidylate synthase TYMS 0.0033
2626 Thymidylate synthase thyA 0.0033
2729 Thymidylate synthase thyA 0.0033
5352 Thymidylate synthase THYA 0.0033
6263 cAMP-dependent protein kinase catalytic subunit alpha PRKACA 0.0032
↑