Amrinone targets phosphodiesterase III (PDE3), an enzyme that hydrolyzes cAMP and cGMP. By inhibiting PDE3, it increases intracellular cAMP levels in cardiac and vascular smooth muscle cells. This leads to increased calcium influx into cardiac cells, enhancing contractility (positive inotropic effect), and vasodilation (vasodilator effect), which reduces cardiac workload.

In vitro and ex vivo, amrinone (Inamrinone) exhibits fold suppression of ADP-induced ischemia aggregation in spots. Amrinone also reduced ischemia in human aortic smooth muscle cells activated by FBS or PDGF culture [4].
In vitro, amrinone is a selective PDE3 inhibitor. Its activity is assessed using enzyme assays with purified PDE3, measuring the inhibition of cAMP hydrolysis. It increases the contractions initiated in the heart by high gain calcium-induced calcium release (CICR). It acts by inhibiting the breakdown of both cAMP and cGMP by PDE3.

Amrinone (Inamrinone) was injected subcutaneously for 14 days at a dose of 10 mg/kg/day for support, and a substantial reduction in neointimal thickness was seen [4].
In vivo, amrinone is a positive inotropic-vasodilator agent used for the short-term treatment of congestive heart failure that does not respond to other drugs. It increases cardiac contractility and acts as a vasodilator. It is effective even in unresponsive, fully digitalized patients.

The in vitro enzyme assay for amrinone measures its ability to inhibit phosphodiesterase III (PDE3) activity. These cell-free assays use purified PDE3 and a substrate such as cAMP or cGMP. The compound's inhibitory potency (IC50) is determined by measuring the reduction in enzyme activity.

In vitro cellular assays for amrinone assess its effects on cAMP levels and cardiac myocyte function. Cardiac myocytes are treated with amrinone, and cAMP levels are measured. Its effects on contractility are assessed in isolated cardiac tissue preparations. These assays demonstrate the compound's functional activity in a relevant cellular context.

In vivo animal studies for amrinone have been conducted in animal models of heart failure to evaluate its efficacy. However, its clinical efficacy has been established in human use for the short-term treatment of congestive heart failure.

Absorption, Distribution and Excretion
In the human body, the primary excretion route is through urine, in the form of aminoketone and several of its metabolites (N-hydroxyacetyl, N-acetic acid, O-glucuronide, and N-glucuronide). 1.2 L/kg [Normal Volunteer] Metabolism/Metabolites Hepatic metabolism. Biological Half-Life 5 to 8 hours
Amrinone is administered intravenously for short-term use. It is not orally active. It is metabolized in the liver and excreted in urine. Its pharmacokinetic properties support its use as an intravenous inotropic agent for the management of severe congestive heart failure.

Protein Binding
10% to 49%
Amrinone is associated with significant adverse effects, including thrombocytopenia, arrhythmias, and hepatotoxicity. Its use is limited to short-term treatment in hospitalized patients. Its safety profile has been established through clinical use.

[1]. The Beneficial Effect of Amrinone on Acute Drug-Induced Heart Failure in the Anaesthetised Dog. Cardiovasc Res. 1985 Aug;19(8):483-94.

[2]. Clinical Use of Amrinone (A Selective Phosphodiesterase III Inhibitor) in Reconstructive Surgery. Plast Reconstr Surg. 2001 Dec;108(7):1931-7.

[3]. Amrinone: A New Non-Glycosidic, Non-Adrenergic Cardiotonic Agent Effective in the Treatment of Intractable Myocardial Failure in Man. Circulation. 1979 Jun;59(6):1098-104.

[4]. [Effects of Amrinone, an Inhibitor of c-AMP-specific Phosphodiesterases, on Neointimal Hyperplasia After Balloon Injury in Rats]. Nihon Yakurigaku Zasshi. 1998 Oct;112(4):267-74.

Amrinone is a 3,4'-bipyridine derivative with amino and keto groups substituted at positions 5 and 6, respectively. It is a pyridine phosphodiesterase 3 inhibitor used to improve the prognosis of patients with congestive heart failure. Amrinone is an EC 3.1.4. (phosphodiester hydrolase) inhibitor and also a cardiovascular drug. Amrinone (or iramirinone) is a type 3 pyridine phosphodiesterase inhibitor used to treat congestive heart failure. Iramirinone is a synthetic bipyridine phosphodiesterase inhibitor with positive inotropic and vasodilatory effects. Iramirinone inhibits type III phosphodiesterase, which is abundant in cardiac and vascular tissues, thereby preventing the degradation of cyclic adenosine monophosphate (cAMP) and increasing the intracellular concentration of this second messenger. Elevated cAMP levels increase myocardial contractility, producing a positive inotropic effect. Although its mechanism of action is not fully elucidated, amrinone causes smooth muscle relaxation, leading to peripheral vasodilation (reducing afterload) and decreased pulmonary vascular resistance (reducing preload). Amrinone is a positive inotropic agent (cardiotonic) with vasodilatory effects, phosphodiesterase 3 (PDE3) inhibitory activity, and the ability to stimulate calcium ion influx into cardiomyocytes. Indications: Used to treat congestive heart failure. Mechanism of Action: Amrinone is a phosphodiesterase 3 (PDE3) inhibitor that leads to increased cAMP and cGMP levels, thereby increasing calcium ion influx, similar to the effect of β-agonists, ultimately enhancing the positive inotropic effect. Pharmacodynamics: Amrinone is a positive inotropic agent with vasodilatory effects, inhibiting phosphodiesterase 3 (PDE3) activity and stimulating calcium ion influx into cardiomyocytes.
Amrinone (CAS 60719-84-8), also known as Inamrinone, is a positive inotropic-vasodilator agent and a selective PDE3 inhibitor. It is used for the short-term treatment of severe congestive heart failure. It has a molecular formula of C10H9N3O and a molecular weight of 187.20. It is available as a prescription medication.

C10H9N3O

187.1980

187.074

60719-84-8

60719-84-8 (free); 75898-90-7 (lactate);

3698

Light yellow to yellow solid powder

1.3±0.1 g/cm3

451.5±45.0 °C at 760 mmHg

294-297ºC

226.9±28.7 °C

0.0±1.1 mmHg at 25°C

1.625

-0.54

2

3

1

14

301

0

RNLQIBCLLYYYFJ-UHFFFAOYSA-N

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)

3-amino-5-pyridin-4-yl-1H-pyridin-2-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~16.67 mg/mL (~89.05 mM)

Solubility in Formulation 1: ≥ 1.67 mg/mL (8.92 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)