Bishydroxycoumarin dicoumarol

Bishydroxycoumarin (dicoumarol) is a natural occurring anticoagulant found in sweet clover. A number of coumarin derivatives have been synthesized as anticoagulants, warfarin, phenprocoumon and acenocoumarol being most frequently used. The nonpolar carbon substituent at the 3 position required for activity is asymmetrical. The enantiomers differ in both pharmacokinetic and pharmacodynamic properties. The coumarins are marketed as racemic mixtures. 

The coumarins were first discovered in Wisconsin, when bleeding in cattle was found to be due to the consumption of bruised sweet clover in the 1920s (1). The causative agent, dicoumarol, was isolated in 1940, and a range of related compounds was then synthesized, the most popnlar of which proved to be warfarin (named after the Wisconsin Alumni Research Foundation). Other conmarins that have been used are acenocoumarol (nicoumalone), bishydroxycoumarin, dicoumarol, ethyl biscoumacetate, and phenproconmon. 

Rgure 10.10 Plasma levels of bishydroxycoumarin (BHC), also known as dicoumarol, in 6 subjects after a 300 mg oral dose with water (solid line), magnesium hydroxide (dotted line) or aluminium hydroxide (dashed line). Closed data points represent a significant difference from control. 

It has been known since 1921 that cattle eating spoiled sweet clover hay often would die from uncontrollable bleeding after suffering a very minor injury. This discovery and other subsequent findings eventually led to the isolation of bishydroxycoumarin (i.e., dicoumarol) in 1934 by Link and Campbell and its use in humans in 1954 as the first orally active anticoagulant drug (21). 

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