Amrinone
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| Trade names | Inocor |
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Intravenous |
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| Bioavailability | n/a |
| Protein binding | 10 to 49% |
| Metabolism | Hepatic |
| Biological half-life | 5 to 8 hours |
| Excretion | Renal (63%) and fecal (18%) |
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| ECHA InfoCard | 100.056.700 |
| Chemical and physical data | |
| Formula | C10H9N3O |
| Molar mass | 187.198 g/mol |
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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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