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Drug-Target Interaction

Drug

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PubChem ID:4197
Structure:
Synonyms:
"1,6-dihydro-2-methyl-6-oxo-(3,4′-bipyridine)-5-carbonitrile"
(3,4'-BIPYRIDINE)-5-CARBONITRILE, 1,6-DIHYDRO-2-METHYL-6-OXO-
(3,4'-Bipyridine)-5-carbonitrile, 6-dihydro-2-methyl-6-oxo-
1,6-Dihydro-2-methyl-6-oxo(3,4'-bipyridine)-5-carbonitrile
1,6-Dihydro-2-methyl-6-oxo-(3,4′-bipyridine)-5-carbonitrile
1,6-Dihydro-2-methyl-6-oxo-(3,4'-bipyridine)-5-carbonitrile
1,6-Dihydro-2-methyl-6-oxo-3,4-bipyridine-5-carbonitrile
1,6-Dihydro-2-methyl-6-oxo-[3,4'-bipyridine]-5-carbonitrile
111GE027
2-methyl-6-oxo-1,6-dihydro-3,4'-bipyridine-5-carbonitrile
3-Cyano-6-methyl-5-(4-pyridyl)-2-pyridone
6-methyl-2-oxo-5-pyridin-4-yl-1H-pyridine-3-carbonitrile
6-Methyl-5-(4-pyridyl)-2-pyridone-3-carbonitrile
78415-72-2
AB00514027
AC-4730
AC1L1HMP
AC1Q2EBX
Ambap5086
BIDD:GT0197
BPBio1_001156
BRN 3546821
BSPBio_001050
C07224
C12H9N3O
CAS-78415-72-2
CCG-101020
CCG-204822
CCRIS 3795
CHEBI:50693
CHEMBL189
Corotrop
Corotrope
CPD000058475
D00417
DB00235
EINECS 278-903-6
EN002063
EU-0100737
HMS1571E12
HMS2051L10
HMS2090J14
HMS2098E12
HMS2234A23
HMS3262C16
I06-0259
Lopac-M-4659
Lopac0_000737
LS-44610
M 4659
M1663
M4659_SIGMA
Milrila
Milrila (TN)
Milrinona
Milrinona [Spanish]
Milrinone
Milrinone (JAN/USAN/INN)
Milrinone Lactate
MILRINONE LACTATE IN DEXTROSE 5% IN PLASTIC CONTAINER
Milrinone [USAN:BAN:INN]
Milrinone, Primacor
Milrinone-Supplied by Selleck Chemicals
Milrinonum
Milrinonum [Latin]
MLS000028818
MLS001424052
NCGC00015675-01
NCGC00015675-02
NCGC00015675-03
NCGC00015675-04
NCGC00015675-05
NCGC00015675-06
NCGC00015675-07
NCGC00015675-08
NCGC00015675-09
NCGC00025189-01
NCGC00025189-02
NCGC00025189-03
NCGC00164390-01
Prestwick0_001065
Prestwick1_001065
Prestwick2_001065
Prestwick3_001065
Primacor
PRIMACOR IN DEXTROSE 5% IN PLASTIC CONTAINER
S2484_Selleck
SAM001246611
SBB055743
SMR000058475
SPBio_002965
Tocris-1504
UNII-JU9YAX04C7
WIN 47203-2
Win-47203
Win-47203-2
YM 018
ZINC09224016
ATC-Codes:
Side-Effects:
Side-EffectFrequency
anaphylactic shock0.0010
tremor0.0010
thrombocytopenia0.0010
hypokalemia0.0010
headaches0.0010
rash0.0010
bronchospasm0.0010
ventricular tachycardia0
hypotension0
shock0
angina pectoris0
chest pain0
tachycardia0
ventricular fibrillation0

Target

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Uniprot ID:Q62710_RAT
Synonyms:
Nitric oxide synthase
EC-Numbers:-
Organism:Rat
Rattus norvegicus
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

8621775
Nitric oxide synthase (NOS3) and contractile responsiveness to adrenergic and cholinergic agonists in the heart. Regulation of NOS3 transcription in vitro and in vivo by cyclic adenosine monophosphate in rat cardiac myocytes.. L Belhassen; R A Kelly; T W Smith; J L Balligand (1996) The Journal of clinical investigation display abstract
Cardiac myocytes express the nitric oxide synthase isoform originally identified in constitutive nitric oxide synthase cells (NOS3), which mediates the attenuation by muscarinic cholinergic agonists of beta-adrenergic stimulation of L-type calcium current and contractility in these cells. However, calcium current and contractility in these cells. However, the reciprocal regulation of NOS3 activity in myocytes by agents that elevate cAMP has not been reported. In this study, we show that NOS3 and mRNA and protein levels in cardiac myocytes are reduced both in vitro after treatment with cAMP elevating drugs, and in vivo after 3 d of treatment with milrinone, a type III cAMP phosphodiesterase inhibitor. This effect on NOS3 activity by cAMP is cell type specific because treatment of cardiac microvascular endothelial cells in vitro or in vivo did not decrease NOS3 mRNA or protein in these cells. NOS3 downregulation in myocytes appeared to be at the level of transcription since there was no modification of NOS3 mRNA half-life by agents that increase intracellular cAMP. To determine the functional effects of NOS3 downregulation, we examined the contractile responsiveness of isolated electrically paced ventricular myocytes, isolated from animals that had been treated in vivo with milrinone, to the beta-adrenergic agonist isoproterenol and the muscarinic cholinergic agonist carbamylcholine. There was no difference in baseline contractile function in cells that had been pretreated with cAMP elevating agents compared to controls, but cells exposed to milrinone in vivo exhibited an accentuation in their contractile responsiveness to isoproterenol compared to controls and a loss of responsiveness to carbamylcholine. Downregulation of myocyte NOS3 by sustained elevation of cAMP may have important implications for the regulation of myocardial contractile state by the autonomic nervous system.