Revaprazan (trade name Revanex) is a drug that reduces gastric acid secretion and is used for the treatment of gastritis and acid-related disease. It acts as an acid pump antagonist (potassium-competitive acid blocker) that reversibly inhibits H+, K+-ATPase by binding to the K+-binding site of the pump, thereby causing fewer side effects, compared with the irreversible proton pump inhibitors. Revaprazan is approved for use in Korea, but is not approved in Europe or the United States.

Benfluorex under trade name Mediator was launched in 1976 for controlling blood sugar levels in people with type 2 diabetes. In 2009 this drug together with others medicines containing it was withdrawn because of the risk of heart valve disease. The mechanisms by which benfluorex reduces hepatic gluconeogenesis are markedly different from those of metformin, the main antidiabetic compound used in the world. It was suggested that inhibition of gluconeogenesis by benfluorex was, at least in part, due to a decrease in mitochondrial β-oxidation. First, benfluorex decreased acetyl-CoA concentration, which in turn would reduce pyruvate carboxylase activity and release its inhibitory effect on pyruvate dehydrogenase. Second, benfluorex decreased both the ATP-to-ADP and the NAD+-to-NADH ratios, leading to a reduced gluconeogenic flux at the level of 3-phosphoglycerate kinase and GAPDH. Changes in cellular redox state represent probably the main mechanism by which benfluorex reduces glucose production in hepatocytes.

Azalanstat is a synthetic imidazole. It has been shown to inhibit cholesterol synthesis in HepG2 cells, human fibroblasts, hamster hepatocytes and hamster liver, by inhibiting the cytochrome P450 enzyme lanosterol 14 alpha-demethylase. In hamsters it lowered serum cholesterol in a dose-dependent manner. Azalanstat preferentially lowered low density lipoprotein (LDL) cholesterol and apo B relative to high density lipoprotein (HDL) cholesterol and apo A-1. Azalanstat inhibited hepatic microsomal hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity in hamsters in a dose-dependent manner and this was highly correlated with serum cholesterol lowering. In vitro studies with HepG2 cells indicated that this modulation of reductase activity was indirect, occurring at a post-transcriptional step. Azalanstat has been in preclinical phase for the treatment of hyperlipidaemia but this research has been discontinued.

Fenoctimine is a nonanticholinergic inhibitor of gastric acid secretion in dogs and rats. Fenoctimine was more potent than cimetidine in the reduction of basal acid secretion in the gastric fistula rat and inhibited the production of gastric acid stimulated by histamine, gastrin tetrapeptide or bethanechol in the chronic gastric fistula dog. This compound is not an H2-antagonist but does inhibit the H+/K+-ATPase of hog gastric mucosa. The in vitro metabolism of fenoctimine by rat liver homogenates resulted in the oxidation of the aliphatic chain at the seven carbon, initially to an alcohol and then to a ketone. The unexpectedly weak effect of fenoctimine as a gastric antisecretory agent in humans, as well as anticholinergic effects, may be due to its extensive metabolism, which is different from that seen in dog and rat. The development of fenoctimine has been discontinued for unspecified reason.

Lidamidine, also known as WHR-1142A and Lidaral, is an alpha2-adrenergic receptor agonist that inhibits intestinal secretion, reduces intestinal transit, and inhibits smooth muscle contraction. Lidamidine hydrochloride is used to treat diarrhoea and other gastrointestinal disorders. Lidamidine’s intestinal antisecretory effects are mediated through the activation of peripheral alpha-2 adrenoceptors. Lidamidine crosses the blood brain barrier poorly and is therefore devoid of the centrally mediated alpha-2 effects that have limited the use of other alpha-2 adrenoceptor agonists in the intestinal tract.

Buformin (1-butylbiguanide) is an oral antidiabetic drug of the biguanide class. AMPK activator. AMPK is a potential therapeutic target in the prevention and the treatment of type 2 diabetes and insulin resistance. Major classes of antidiabetic drugs have been reported to activate AMPK. Buformin exerts its anti-tumorigenic activity via activation of AMPK and inhibition of the mTOR signaling pathways in endometrial cancer cells. Toxicity: guinea pig LD50 subcutaneous 18 mg/kg; mouse LD50 intraperitoneal 140 mg/kg and 300 mg/kg oral. Buformin was withdrawn from the market in many countries due to an elevated risk of causing lactic acidosis.

Boxidine (1-[2-[[4′-(Trifluoromethyl)-4-biphenylyl]oxy]ethyl]pyrrolidine) is an inhibitor of 3β-hydroxysteroid-Δ7-reductase (DHCR7) thereby it affects cholesterol biosynthesis. Boxidine induces the accumulation of desmosterol.

Azacosterol (Ornitrol, 20,25-diazacholesterol dihydrochloride, SC 12937) is a cholesterol-lowering drug (hypocholesteremic) which was marketed previously but has since been discontinued. Azacosterol is a sterol derivative of cholesterol with two nitrogen atoms replacing two carbon atoms that acts as a hypocholesteremic agent by blocking delta-24-reductase. Azacosterol has the unintended side effect of causing myotonia. It is an avian contraceptive compound, which reduces fertility by inhibiting cholesterol synthesis. Azacosterol is also useful in the control of rodent populations.