Amrinone

Amrinone (CAS No. 60719-84-8) is a selective phosphodiesterase Ⅲ (PDE3) inhibitor that inhibits cAMP degradation and increases intracellular cAMP levels, exhibiting positive inotropic + vasodilatory effects. It is a typical non-glycoside, non-catecholamine cardiotonic and vasodilator, mainly used in heart failure and cardiovascular function research.

At the enzymatic level, Amrinone inhibits PDE3 with an IC₅₀ ≈ 19.5 μM. In isolated cat papillary muscle experiments, it significantly increases contractile tension and contraction velocity, demonstrating a positive inotropic effect. It also has regulatory effects on platelets and vascular smooth muscle: in vitro and in rat ex vivo models, it dose-dependently inhibits ADP-induced platelet aggregation; in FBS- or PDGF-stimulated human aortic smooth muscle cells, it can inhibit cell proliferation, suggesting potential applications in studies of vascular remodeling, atherosclerosis/restenosis, and related areas.

In whole-animal models, Amrinone (1–10 mg/kg) can significantly increase myocardial contractility and heart rate in anesthetized and conscious dogs, showing strong positive inotropic activity; in rats, subcutaneous injection at 10 mg/kg/day for 14 consecutive days markedly reduces neointimal thickness, supporting its anti-vascular remodeling effects through inhibition of smooth muscle proliferation and platelet aggregation. Overall, Amrinone is both a classic PDE3-inhibiting cardiotonic vasodilator and an important tool compound for studying cardiac function regulation, platelet aggregation, and vascular smooth muscle proliferation.

References:

[1] Alousi AA, Farah AE, Lesher GY, Opalka CJ Jr. Cardiotonic activity of amrinone--Win 40680 [5-amino-3,4'-bipyridine-6(1H)-one]. Circ Res. 1979 Nov;45(5):666-77. doi: 10.1161/01.res.45.5.666. PMID: 39684.

[2] LeJemtel TH, Keung E, Sonnenblick EH, Ribner HS, Matsumoto M, Davis R, Schwartz W, Alousi AA, Davolos D. 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. doi: 10.1161/01.cir.59.6.1098. PMID: 436202.

[3] Alousi AA, Canter JM, Fort DJ. The beneficial effect of amrinone on acute drug-induced heart failure in the anaesthetised dog. Cardiovasc Res. 1985 Aug;19(8):483-94. doi: 10.1093/cvr/19.8.483. PMID: 4042115.

[4] Hachisu M, Nomura M, Fujishima K. [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. Japanese. doi: 10.1254/fpj.112.267. PMID: 9866844.

[5] Ichioka S, Nakatsuka T, Ohura N, Sato Y, Harii K. Clinical use of amrinone (a selective phosphodiesterase III inhibitor) in reconstructive surgery. Plast Reconstr Surg. 2001 Dec;108(7):1931-7. doi: 10.1097/00006534-200112000-00013. PMID: 11743379.