Carbenoxolone

Carbenoxolone

Systematic (IUPAC) name
(3β)-3-[(3-carboxypropanoyl)oxy]-11-oxoolean-12-en-30-oic acid OR (2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-(3-carboxypropanoyloxy)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylic acid
Clinical data
AHFS/Drugs.com	International Drug Names
Identifiers
CAS Number	5697-56-3
ATC code	A02BX01 (WHO)
PubChem	CID 636403
IUPHAR/BPS	4151
DrugBank	DB02329
ChemSpider	552190
UNII	MM6384NG73
ChEMBL	CHEMBL499915
Chemical data
Formula	C34H50O7
Molar mass	570.765 g/mol
SMILES O=C(O)CCC(=O)O[C@H]4CC[C@@]3([C@H]5C(=O)/C=C2/[C@@H]1C[C@](C(=O)O)(C)CC[C@]1(C)CC[C@]2([C@@]5(CC[C@H]3C4(C)C)C)C)C
InChI InChI=1S/C34H50O7/c1-29(2)23-10-13-34(7)27(32(23,5)12-11-24(29)41-26(38)9-8-25(36)37)22(35)18-20-21-19-31(4,28(39)40)15-14-30(21,3)16-17-33(20,34)6/h18,21,23-24,27H,8-17,19H2,1-7H3,(H,36,37)(H,39,40)/t21-,23-,24-,27+,30+,31-,32-,33+,34+/m0/s1 Key:OBZHEBDUNPOCJG-WBXJDKIVSA-N
(what is this?)  (verify)

Carbenoxolone (CBX) is a glycyrrhetinic acid derivative with a steroid-like structure, similar to substances found in the root of the licorice plant. Carbenoxolone is used for the treatment of peptic, esophageal and oral ulceration and inflammation. Electrolyte imbalance is a serious side effect of carbenoxolone when used systemically.^[1]

Carbenoxolone reversibly inhibits the conversion of cortisol to the inactive metabolite cortisone by blocking 11β-hydroxysteroid dehydrogenase (11β-HSD). 11β-HSD also reversibly catalyzes the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. ^[2][3]

Carbenoxolone is a modestly potent, reasonably effective, water-soluble blocker of gap junctions.^[4]

Nootropic effects

Carbenoxolone has also been investigated for nootropic effects.^[5] This research started from an observation that long-term exposure to glucocorticoids may have negative effects on cognition. Carbenoxolone may decrease the amount of active glucocortocoid in the brain, because the drug inhibits 11β-HSD, an enzyme which regenerates cortisol, an active glucocorticoid, from inactive cortisone.

In the research trial investigating this use of carbenoloxone, it was shown that the drug improved verbal fluency in elderly healthy men (aged 55–75). In type 2 diabetics aged 52–70, the drug improved verbal memory. However, potassium-sparing diuretic amiloride was co-administered with carbenoxolone, since carbenoxolone used by itself may cause hypertension by increasing cortisol in the kidneys.

References

1. "Tales of a Dirty Drug: Carbenoxolone, Gap Junctions, and Seizures".
2. "PubChem Compound".
3. "Sigma-Aldrich" (PDF).
4. "Tales of a Dirty Drug: Carbenoxolone, Gap Junctions, and Seizures".
5. Sandeep TC, Yau JL, MacLullich AM; et al. (2004). "11Beta-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics". Proc. Natl. Acad. Sci. U.S.A. 101 (17): 6734–9. doi:10.1073/pnas.0306996101. PMC 404114. PMID 15071189.