First isolated in 1882 by French chemist Léon-Albert Arnaud from Acokanthera ouabaio arrow-poison wood (and achieved by total chemical synthesis in Pierre Deslongchamps's laboratory in 2008), ouabain is a water-soluble cardenolide glycoside.
Ouabain binds the extracellular phosphorylated E2-P conformation of the Na⁺/K⁺-ATPase α subunit, blocking active Na⁺ extrusion and K⁺ import across the plasma membrane.
In cardiomyocytes, raising intracellular Na⁺ slows or reverses the sarcolemmal Na⁺/Ca²⁺ exchanger (NCX), increasing sarcoplasmic reticulum Ca²⁺ stores and contractile force (positive inotropy); in cell physiology, ouabain is the standard reference blocker for quantifying active sodium-pump ATP consumption.