Inamrinone

Amrinone
Clinical data


Trade names	Inocor
AHFS/Drugs.com	International Drug Names
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	Intravenous
ATC code	C01CE01 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	n/a
Protein binding	10 to 49%
Metabolism	Hepatic
Biological half-life	5 to 8 hours
Excretion	Renal (63%) and fecal (18%)
Identifiers
IUPAC name 5-amino-3,4'-bipyridin-6(1H)-one
CAS Number	60719-84-8^Y
PubChem CID	3698
IUPHAR/BPS	7202
DrugBank	DB01427^Y
ChemSpider	3570^Y
UNII	JUT23379TN
KEGG	D00231^Y
ChEMBL	CHEMBL12856^Y
ECHA InfoCard	100.056.700
Chemical and physical data
Formula	C₁₀H₉N₃O
Molar mass	187.198 g/mol
3D model (JSmol)	Interactive image
SMILES O=C2C(/N)=C\C(\c1ccncc1)=C/N2
InChI InChI=1S/C10H9N3O/c11-9-5-8(6-13-10(9)14)7-1-3-12-4-2-7/h1-6H,11H2,(H,13,14)^Y Key:RNLQIBCLLYYYFJ-UHFFFAOYSA-N^Y

Amrinone (INN) or inamrinone (USAN, changed in 2000 to prevent confusion with amiodarone), trade name Inocor, is a pyridine phosphodiesterase 3 inhibitor. It is a drug that may improve the prognosis in patients with congestive heart failure. Amrinone has been shown to increase the contractions initiated in the heart by high gain calcium induced calcium release (CICR). The positive inotropic effect of amrinone is mediated by the selective enhancement of high gain CICR which contributes to the contraction of myocytes by phosphorylation through cAMP dependent protein kinase A (PKA) and Ca²⁺ calmodulin kinase pathways.

Increases cardiac contractility, vasodilator. Acts by inhibiting the breakdown of both cAMP and cGMP by the phosphodiesterase (PDE3) enzyme. There is a long-standing controversy regarding whether the drug actually increases cardiac contractility in diseased myocardium (and therefore whether it is of any clinical use). The issue has been reviewed extensively by Dr Peter Wilmshurst, one of the first cardiologists and researchers to question the drug's efficacy.

PDE III is present in cardiac muscle, vascular smooth muscle and platelets. PDE III degrades the phosphodiester bond in cAMP to break it down. When PDE III is inhibited, cAMP cannot be inactivated. An increase in cAMP with the administration of amrinone in vascular smooth muscle produces vasodilation by facilitating calcium uptake by the sarcoplasmic reticulum (a special type of smooth ER) and decreasing the calcium available for contraction. In myocytes, the increase of cAMP concentration increases in turn the activity of PKA: this kinase improves the Ca²⁺ inward current through the L-type Ca²⁺ channels, which leads to calcium-induced calcium release from the sarcoplasmic reticulum, giving rise to a calcium spark that triggers the contraction; this results in an inotropic effect. Furthermore, PKA phosphorylates and deactivates the phospholambans that inhibit SERCA, which is an enzymatic pump that, to terminate the contraction, removes the Ca²⁺ from the cytoplasm, stores it back in the sarcoplasmic reticulum and promotes the subsequent relaxation as well, producing a lusitropic effect. Both inotropic and lusitropic effects are the reason why amrinone is used to treat heart failure. Amrinone decreases the pulmonary capillary wedge pressure while increasing cardiac output because it functions as an arterial vasodilator and increases venous capacitance while decreasing venous return. There is a net decrease in myocardial wall tension, and O₂ consumption when using amrinone. Amrinone also has beneficial effects during diastole in the left ventricle including relaxation, compliance and filling in patients with congestive heart failure.

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