Proglumide is a drug that inhibits gastrointestinal motility and reduces gastric secretions. It acts as a cholecystokinin antagonist, which blocks both the CCKA and CCKB subtypes. It was used mainly in the treatment of stomach ulcers, although it has now been largely replaced by newer drugs for this application. An interesting side effect of proglumide is that it enhances the analgesia produced by opioid drugs, and can prevent or even reverse the development of tolerance to opioid drugs. This can make it a useful adjuvant treatment to use alongside opioid drugs in the treatment of chronic pain conditions such as cancer, where opioid analgesics may be required for long periods and development of tolerance reduces clinical efficacy of these drugs.

Plaunotol [(2E, 6Z, 10E)-7-hydroxymethyl-3,11,15-trimethyl-2,6,10, 14-hexadecatetraen-1-ol)] is an acyclic diterpene alcohol originally isolated from the plant Croton sublyratus, which is native to southeast Asia. Plaunotol has been used to treat gastritis and gastric ulcers in Japan. Plaunotol increases the prostaglandin production in the gastric mucosa and accelerates ulcer healing. The precise mechanisms underlying the gastroprotective actions by plaunotol are not known. On the other hand, cyclooxygenase (COX)-2 is a key enzyme in PGE(2) production and its induction is thought to have an important role in ulcer healing. Plaunotol induced COX-2 expression and increased PGE(2) production in serum-starved RGM1 cells via activation of the NF-kappaB and CRE sites of Cox-2 gene promoters. In vitro studies showed bactericidal action against H. pylori by increasing membrane fluidity, leading to autolysis and deterioration of cell structure

Voglibose is an alpha glucosidase inhibitor, which was initially marketed in Japan as an improving agent for postprandial hyperglycemia in diabetes mellitus. Later on the drug was approved for the prevention of type 2 diabetes. The drug is available in Asia under the name Basen.

Tiadenol (2,2'-(decamethylenedithio)-diethanol) exrets hepatic peroxisome proliferative activity, it induces peroxisomal enzymes and peroxisome proliferation. Tiadenol is known for its hypolipidemic properties.

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.

Pibutidine hydrochloride (IT-066), a novel histamine H2 receptor antagonist has powerful and long lasting antisecretory and antiulcer effects and is a useful antisecretory drug for treatment of peptic ulcer diseases.

Glyclopyramide (N-p-chlorobenzene sul-fonyl, N'-pyrrolidinourea) marketed under the tradename Deamelin-S is a sulfonylurea drug used in the treatment of diabetes mellitus. It has been marketed in Japan.

Metahexamide (N(3-amino-4-methyl-benzenesulfonyl)-N'-cyclohexylurea) is an oral hypoglycemizing agent. The remarkable hypoglycemizing action of metahexamide is justified by two properties: the slow metabolism and the strongly enhanced peripheral glucose utilization. Metahexamide has been studied in the treatment of diabetes.

Beclobrate is a fibric acid derivative with potent cholesterol- and triglyceride-lowering effects. The effectiveness of the drug has been investigated in a variety of studies including patients with hyperlipidemia types IIa, IIb and IV and patients suffering from secondary hyperlipidemia attributable to diabetes mellitus, liver disease, end-stage renal failure requiring hemodialysis, and kidney transplantation. In general, side-effects of beclobrate therapy are comparable with those of other fibric acid derivatives. Gastrointestinal disturbances, nausea were the major side-effects. Beclobrate has now been withdrawn from the market since the risk of hepatic damage is believed to outweigh the potential benefits of the drug.

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.