Carbenoxolone, a synthetic derivative of glycyrrhetinic acid

Glycyrrhetinic acid

Glycyrrhetinic acid is a pentacyclic triterpenoid derivative of the beta-amyrin type obtained from the hydrolysis of glycyrrhizic acid, which was obtained from the herb liquorice. It is used in flavoring and it masks the bitter taste of drugs like aloe and quinine. It is effective in the treatment...

, is a licensed drug (in the UK

United Kingdom

The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

) for oesophageal

Esophagus

The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...

 ulceration and inflammation. Other uses include treatment of oral and perioral lesions.

Carbenoxolone (aka Carbenoxolone, CBX) is also used as a blocker of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD), of pannexon membrane channels (comprising 6 subunits of pannexin

Pannexin

Pannexins are a family of vertebrate proteins identified by their homology to the invertebrate innexins...

) and the related innexon channels (consisting of invertebrate innexins), and at higher concentrations, as a blocker of connexon

Connexon

In biology, a connexon is an assembly of six proteins called connexins that can be a part of a gap junction channel between the cytoplasm of two adjacent cells. The connexon is actually the hemichannel supplied by a cell on one side of the junction; two connexons from opposing cells normally come...

 channels ("hemichannels" made up of 6 connexin

Connexin

Connexins, or gap junction proteins, are a family of structurally-related transmembrane proteins that assemble to form vertebrate gap junctions . Each gap junction is composed of two hemichannels, or connexons, which are themselves each constructed out of six connexin molecules...

 subunits each) and of gap junctions (2 connexons joined together).

Nootropic effects

Carbenoxolone has also been investigated for nootropic

Nootropic

Nootropics , also referred to as smart drugs, brain steroids, memory enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration...

 effects.

This research started from an observation that long-term exposure to glucocorticoid

Glucocorticoid

Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

s may have negative effects on cognition. Carbenoxolone may decrease the amount of active glucocortocoid in the brain, because the drug inhibits 11Beta-hydroxysteroid dehydrogenase type 1, an enzyme which activates cortisol

Cortisol

Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

 from cortisone

Cortisone

Cortisone is a steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to corticosterone. It is used to treat a variety of ailments and can be administered intravenously, orally,...

, a glucocorticoid. 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

Potassium-sparing diuretic

Potassium-sparing diuretics are diuretic drugs that do not promote the secretion of potassium into the urine.They are used as adjunctive therapy, together with other drugs, in the treatment of hypertension and management of congestive heart failure....

 amiloride

Amiloride

Amiloride is a potassium-sparing diuretic, first approved for use in 1967 , used in the management of hypertension and congestive heart failure. Amiloride was also tested as treatment of cystic fibrosis, but it was revealed inefficient in vivo due to it's short time of action, therefore...

 was co-administered with carbenoxolone, since carbenoxolone used by itself may cause hypertension

Hypertension

Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

by increasing cortisol in the kidneys.