Disease relevance of carbenoxolone

• A double blind trial involving 21 patients on carbenoxolone and 23 patients on placebo was conducted under endoscopic control to assess the healing of duodenal ulcers over a period of 6 weeks [1].
• Side effects of carbenoxolone therapy in the form of weight gain, rise in diastolic blood pressure and hypokalaemia were observed, but with adequate monitoring and appropriate countermeasures, no patient suffered any ill effects [1].
• Topical carbenoxolone for orofacial herpes simplex infections [2].
• Beginning 1 week prior to administration of 35 mg N-methyl-N-nitrosourea per kg body weight, groups of 20 female Sprague-Dawley rates were fed AIN-76A diet supplemented with DHEA alone (800 or 400 mg/kg diet), DHEA + tamoxifen (80 or 40 microgram/kg diet), DHEA + carbenoxolone (3500 or 1750 mg/kg diet), or DHEA + tamoxifen + carbenoxolone [3].
• Serum carbenoxolone levels were similar in patients whose gastric ulcers had or had not healed after four weeks' treatment [4].

Psychiatry related information on carbenoxolone

• This increase was associated with a comparable impairment in motor activity; however, the therapeutic index of combined treatment of antiepileptic drugs with carbenoxolone was more favourable than the combination with glycyrrhizin or saline [5].

High impact information on carbenoxolone

• Consistent with a role of pannexin 1 as an ATP release channel, ATP release by erythrocytes was attenuated by the gap junction blocker carbenoxolone [6].
• The 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone (1 mumol/L) completely blocked conversion in both directions [7].
• Compound A, even in the presence of carbenoxolone, effected other glucocorticoid actions by inhibiting cell growth and potentiating angiotensin II-stimulated inositol phosphate formation [7].
• Second, the gap-junction blocker carbenoxolone greatly reduces exogenous 3H-glycine accumulation into the bipolar cells but not the amacrine cells [8].
• 11-Dehydrocorticosterone also potentiated kainate neurotoxicity; this effect was lost, however, if 11 beta-HSD was inhibited with carbenoxolone [9].

Chemical compound and disease context of carbenoxolone

• Because synchrony in some networks is mediated by gap junctions, we examined whether the gap junction blockers heptanol, octanol, carbenoxolone, and mefloquine suppress tremor in the mouse harmaline model, and performed an open-treatment clinical study of mefloquine for essential tremor [10].
• To determine whether the addition of carbenoxolone to a cimetidine regimen would prevent mucus deficiency in patients with duodenal ulcer, we compared the effect of combined therapy with the effects of treatment with cimetidine alone and carbenoxolone alone [11].
• To test this prediction, and estimate the relative magnitude of this effect on third-order cells, we recorded light responses in mouse ganglion cells under photopic conditions and applied two gap junction antagonists, carbenoxolone and the structurally related 18beta-glycyrrhetinic acid (GA) [12].
• Carbenoxolone did not produce a cushingoid appearance or increase body weight, blood pressure, blood glucose or plasma insulin levels [13].
• Using a rat model involving low dose corticosterone treatment, we found that carbenoxolone neither potentiated nor inhibited the modest increases in blood pressure or reductions in weight gain caused by steroid treatment [14].

Biological context of carbenoxolone

• Carbenoxolone may exert its metabolic effects systemically, but its ulcer-healing effects topically; additional studies are needed to test this hypothesis [4].
• Changes in the plasma clearance and protein binding of carbenoxolone with age, and their possible relationship with adverse drug effects [15].
• We obtained Percoll-purified human placental and chorion trophoblast cells from uncomplicated term pregnancies, cultured them for 72 h, then treated the cells with cortisol (100 nmol/L), cortisone (1 micromol/L), or DEX (100 nmol/L), in the presence or absence of carbenoxolone (CBX, 800 nmol/L), an 11beta-HSD inhibitor, for 24 h [16].
• RESULTS: Carbenoxolone triggered the morphological change of activated HSCs without inducing apoptosis [17].
• Carbenoxolone induces oxidative stress in liver mitochondria, which is responsible for transition pore opening [18].

Anatomical context of carbenoxolone

• The light-responsive units formed an extensive network that could be uncoupled by application of the gap junction blocker carbenoxolone [19].
• Like microsomal RoDH, the recombinant enzyme recognized as substrate retinol bound to cellular retinol-binding protein, had higher activity with NADP rather than NAD, was stimulated by ethanol or phosphatidylcholine, was not inhibited by 4-methylpyrazole, was inhibited by phenylarsine oxide and carbenoxolone and localized to microsomes [20].
• This results in an increased supply of young mucous cells; if this also proves to be true in human gastric mucosa, it may be relevant to the therapeutic effect of carbenoxolone [21].
• Effect of carbenoxolone on the synthesis of glycoproteins and DNA in rat gastric epithelial cells [21].
• These effects of carbenoxolone require intact maternal adrenal glands suggesting that inhibition of feto-placental 11 beta-HSD 2 is key [22].

Associations of carbenoxolone with other chemical compounds

• Cortisol was converted to inactive cortisone in mixed synovial cells from RA and OA patients, which was largely inhibited by carbenoxolone (11beta-HSD1 and 11beta-HSD2 inhibitor) [23].
• The rate of incorporation of tritiated galactose, glucosamine, serine, and sulphate in surface mucous cells, studied by autoradiography, was not affected by the addition of carbenoxolone to the drinking water [21].
• Glycyrrhizic acid, the active ingredient in licorice, and its metabolite carbenoxolone are potent inhibitors of human 11 beta-hydroxysteroid dehydrogenase and bacterial 3 alpha, 20 beta-hydroxysteroid dehydrogenase (3 alpha, 20 beta-HSD) [24].
• Vascular smooth muscle relaxation with sodium nitroprusside was not inhibited by carbenoxolone [25].
• Mechanical denudation of the endothelium obviated enhancement of Ang II contractions by carbenoxolone, suggesting interaction of carbenoxolone with the endothelium [25].

Gene context of carbenoxolone

• Prenatal glucocorticoid exposure leads to offspring hyperglycaemia in the rat: studies with the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone [22].
• Here we show that administration of carbenoxolone, an inhibitor of placental 11 beta-HSD 2, to pregnant rats, leads to a significant reduction in average birth weight (20% fall) [22].
• If the enzyme is congenitally inactive, or blocked by carbenoxolone, physiologic glucocorticoids act as MR agonists in such tissues [26].
• The 11 beta OHSD inhibitor (carbenoxolone) inhibited DHCS-mediated alpha 1- and beta 1-mRNA induction, whereas it caused no effect on CS-mediated alpha 1- or beta 1-mRNA induction [27].
• Inhibition of 11betaHSD-2 activity by carbenoxolone during NaCl restriction stimulated NHE-3 expression in colon [28].

Analytical, diagnostic and therapeutic context of carbenoxolone

• Blood flow, as measured by radioactive microspheres, was not changed by carbenoxolone treatment, but subsequent exposure to isotonic HC1 caused an abrupt rise in flow [29].
• In two randomized, double-blind, placebo-controlled crossover studies, administration of the 11beta-HSD inhibitor carbenoxolone (100 mg three times per day) improved verbal fluency (P < 0.01) after 4 weeks in 10 healthy elderly men (aged 55-75 y) and improved verbal memory (P < 0.01) after 6 weeks in 12 patients with type 2 diabetes (52-70 y) [30].
• The influence of carbenoxolone on the synthesis of glycoproteins in the surface mucous cells and the production of new cells in the rat gastric mucosa was studied by means of a vascular perfusion system [21].
• The sugar composition (determined by gas-liquid chromatography) of the gastric glycoproteins (isolated by centrifugation in CsCl), was not changed in carbenoxolone-treated rats [21].
• Some studies suggest that carbenoxolone adds to the effect of hospitalisation and bed rest on ulcer healing [31].

References