Terpenoid Derivatives as Anti-Ulceric Compounds

Recent clinical trials have revealed that two terpenoid derivatives of quite different chemical constitutions may hold some promise as useful chemotherapeutic agents in the treatment of gastric ulcers, although accurate assessment of their therapeutic potentialities must await the fullness of time. These compounds are the disodium salt of the hemisuccinate ester (LXVIII) of 18 -glycyr-rhetinic acid (approved name Carbenoxolone sodium) [505 a] and the geranyl ester (LXIX) of farnesylacetic acid (approved name Gefarnate). 

Carbenoxolone sodium was prepared essentially from considerations [506] of the concept of drug latentiation [507, 508] in order to secure a water-solubi- 

Used form of the virtually insoluble glycyrrhetinic acid (syn. glycyrrhetic acid) in the course of intensive investigations [8, 10, 509] into the reputed anti-ulceric properties [510] of crude extracts of Uquorice. At the time considerable controversy developed as to the efficacy [511-523] or lack of efficacy [524-530] of glycyrrhetinic acid as a topical agent when appUed to certain inflammatory 

The anti-ulceric properties of Carbenoxolone sodium throw open not only the question of its precise mechanism of action, but also the question of the exact relationship of its activity to the activities of certain other triterpenoids [539]. These include/ -amyrin, which is stated [540] to exhibit anti-inflammatory properties similar to those of the glucocorticoids aescin, the complex glycoside of 16-acetyl-21-tiglyloxyprotoaescigenin (LXX) [541] which exhibits anti-oede-matous properties [542-546] without showing beneficial effects on connective 

Initially it was found that Carbenoxolone sodium did not show the same efficacy against duodenal ulcers that it seemed to show against gastric ulcers but as a result of metabolic studies in the rat [564] indicating virtually complete absorption of glycyrrhetinic acid from the stomach and its metabolism by the liver so that only metabolic end-products being secreted into the bile could be coming into contact with the duodenum, presentation of Carbenoxolone sodium in positioned-release capsule form has been initiated as an approach to the treatment of duodenal ulcers. 

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