Systematic (IUPAC) name
Clinical data
AHFS/ International Drug Names
Pregnancy cat. C(US)
Legal status -only (US)
Routes Intravenous
Pharmacokinetic data
Bioavailability n/a
Protein binding 10 to 49%
Metabolism Hepatic
Half-life 5 to 8 hours
Excretion Renal (63%) and fecal (18%)
CAS number 60719-84-8 YesY
ATC code C01CE01
PubChem CID 3698
DrugBank DB01427
ChemSpider 3570 YesY
KEGG D00231 YesY
Chemical data
Formula C10H9N3O 
Mol. mass 187.198 g/mol
SMILES eMolecules & PubChem
 YesY(what is this?)  (verify)

Amrinone (INN) or inamrinone (USAN, changed in 2000 to prevent confusion with amiodarone[1]), trade name Inocor, is a pyridine phosphodiesterase 3 inhibitor[2]. It is a drug that may improve the prognosis in patients with congestive heart failure[3]. Amrinone has been shown to increase the contractions initiated in the heart by high gain calcium induced calcium release (CICR)[4]. 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[4].



It is used in the treatment of congestive heart failure.

It has been studied for use before coronary artery bypass surgery.[5]


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[6].

PDE- III inhibition and cardiac function

PDE III is present in cardiac muscle, vascular smooth muscle and platelets. PDE III degrades the phosphodiester bond in cAMP to break it down [7] [8]. 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 [9] [7]. Since amrinone inhibits PDE III, it also inhibits the L type Ca2+ current in myocytes as well as facilitating an increase in Ca2+ uptake by the sarcoplasmic reticulum (SR) [4]. This may contribute to its positive inotropic effect on cardiac myocytes [4]. 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 [7]. 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 [7].


Short-term management of severe CHF (not used long term because of increased mortality, probably due to heart failure).

How Amrinone is used to correct Congestive Heart Failure

Congestive heart failure (CHF) is characterized by a reduction in ventricular performance and abnormalities in peripheral circulation and organs [8]. A reduced release of endothelium derived relaxing factor (EDRF) causes a decrease in the stimulation of guanylate cyclase and cyclic GMP (cGMP) levels fall in vascular smooth muscle. This impairs relaxation in the vasculature and is a part of the vicious cycle of CHF[8]. Patients with CHF have a down-regulation of their β-1 adrenergic receptors which alters their ability to activate intracellular adenylate cyclase which catalyzes cAMP formation [7]. cAMP is the second messenger that controls the level of calcium available to allow the heart to contract. An IV administration of amrinone has been shown to increase cardiac output (CO) and stroke volume (SV) while concurrently reducing the filling pressure of the left ventricle and decreasing the resistance in the peripheral vasculature [3] [10] [11]. This does not lead to an increase in heart rate or blood pressure [3] [10] [11] . This improvement in performance of the ventricles is likely to result from a direct stimulation of the depressed myocardium as well as a decrease in peripheral vascular resistance [12].


Patients with history of hypersensitivity to the drug.


May increase myocardial ischemia. Blood pressure, pulse, and EKG should be constantly monitored. Amrinone should only be diluted with normal saline or 1/2 normal saline; no dextrose solutions should be used. Furosemide should not be administered into an IV line delivering Amrinone.

Side effects

Thrombocytopenia is the most prominent and dose-related side effect, but it is transient and asymptomatic. Nausea, diarrhoea, hepatotoxicity, arrhythmias and fever are other adverse effects.


IV bolus and infusion as described earlier.

Pediatric dosage

Safety in children has not been established.

Amrinone discovery and progression

Early studies in patients with heart failure showed that amrinone produced short-term hemodynamic improvement, but had limited long-term clinical benefit [9]. Some serious side effects of long term administration included sustained ventricular tachycardia resulting in circulatory collapse, worsening myocardial ischemia, acute myocardial infarction, and worsening congestive heart failure [9] [13]. Amrinone has good absorption from the gastrointestinal tract [14]and may lead to some gastrointestinal upset when taken orally. The oral form of the drug is no longer in use.[13] Currently, only acute intravenous administration takes place [13]. The effects of amrinone vary widely with species and experimental condition; therefore inotropic effects are variable [4]. A loss in sensitivity to PDE III inhibitors has been observed in end stage heart failure in humans and thus other treatment options may be necessary to improvement in these stages [4].


  1. ^ "Amrinone Becomes Inamrinone". USP Quality Review (United States Pharmacopeia) 73. March 2000. 
  2. ^ Hamada Y, Kawachi K, Yamamoto T, et al. (August 1999). "Effects of single administration of a phosphodiesterase III inhibitor during cardiopulmonary bypass: comparison of milrinone and amrinone" ([dead link]). Japanese circulation journal 63 (8): 605–9. doi:10.1253/jcj.63.605. PMID 10478810. 
  3. ^ a b c Klein N.A., Siskind S.J., Frishman W.H., Sonnelblick E.H., LeJemtel T.H. (1981). "Hemodynamic Comparison of Intravenous Amrinone and Dobutamine in Patients With Chronic Congestive Heart Failure". American Journal of Cardiology 48: 170-175. 
  4. ^ a b c d e f Xiong W., Ferrier G.R., Howlett S.E. (2004). "Diminished Inotropic Response to Amrinone in Ventricular Myocytes from Myopathic Hamsters Is Linked to Depression of High-Gain Ca2+-Induced Ca2+ Release". The Journal of Pharmacology and Experimental Therapeutics 310: 761-773. 
  5. ^ Kikura M, Sato S (January 2002). "The efficacy of preemptive Milrinone or Amrinone therapy in patients undergoing coronary artery bypass grafting". Anesth. Analg. 94 (1): 22–30, table of contents. doi:10.1097/00000539-200201000-00005. PMID 11772795. 
  6. ^ Wilmshurst P. The HealthWatch Award 2003: Dr Peter Wilmshurst - "Obstacles to honesty in medical research". 
  7. ^ a b c d e Levy J.H., Ramsay J., Bailey J.M. (1990). "Levy J.H., Ramsay J., Bailey J.M.". Journal of Cardiothoracic Anesthesia (4): 7-11. 
  8. ^ a b c LeJemtel T.H., Scortichini D., Levitt B., Sonnenblick E.H. (1989). "Effects of Phosphodiesterase Inhibition on Skeletal Muscle Vasculature". American Journal of Cardiology 3: 27-30. 
  9. ^ a b c Packer M., Medina N., Yushak M. (1984). "Hemodynamic and clinical limitations of long- term inotropic therapy with amrinone in patients with severe chronic heart failure". Circulation 70: 1038-1047. 
  10. ^ a b Carabello B.A. (1980). "Effects of Amrinone on Myocardial Energy Metabolism and Hemodynamics in Patients with Severe Congestive Heart Failure Due to Coronary Artery Disease". Circulation 62: 28-34. 
  11. ^ a b Konstam M.A., Cohen S.R., Weiland D.S., Martin T.T., Das D., Isner J.M., Salem D.N. (1986). "Relative Contribution of Inotropic and Vasodilator Effects of Amrinone- induced Hemodynamic improvement in congestive heart failure". American Journal of Cardiology 57: 242-248. 
  12. ^ LeJemtel T.H., Keung E., Ribner H.S., Davis R., Wexler J., Blaufox D.M., Sonnenblick E.H. (1980). "Sustained Beneficial Effects of Oral Amrinone on Cardiac and Renal Function in Patients With Severe Congestive Heart Failure". American Journal of Cardiology (45): 123-129. 
  13. ^ a b c Rettig G., Sen S., Frohlig G., Schieffer H., Bette L. (1986). "Withdrawal of long-term amrinone therapy in patients with congestive heart failure: a placebo controlled trial". European Heart Journal 7: 628-631. 
  14. ^ Alousi A.A., Farah A.E., Lesher G.Y., Opalka C.J. (1979). "Cardiotonic Activity of Amrinone- Win 40680 [5-Amino-3, 4- bipyridin- 6(1H)-one].". Circultaion (45): 666-677.