Tiotidine is a controversial histamine H2 receptor ligand with negligible activity against H1- and H3- receptors. It was found that tiotidine behaves as an inverse agonist in U-937 cells, diminishing basal cAMP levels. Tiotidine showed two binding sites, one with high affinity and low capacity and the other with low affinity and high capacity. Tiotidine is currently in use as a radioligand in histamine H2-receptor binding studies. Compared to cimetidine, tiotidine appears to be approximately eight times more potent on a molar basis than cimetidine as an inhibitor of acid secretion, and the tiotidine effect is more prolonged. It was developed for the treatment of peptic ulcer.

Lodinixil is antilipidaemic and anti-atherosclerotic agent. It had been in the preclinical phase for the hyperlipidemia treatment but this development was discontinued.

Tomoglumide (CR 1392) is the glutaramic acid-derivative. It is a cholecystokinin (CCK) receptor antagonist. The CR 1392 had an inhibitory effect on both CCK-octapeptide (CCK-8)-stimulated immunoreactive insulin (IRI) release and exocrine secretion in the isolated perfused rat pancreas. The concentration of CR 1392 that caused half-maximal inhibition of CCK-8-stimulated IRI release was 300 times lower than that of exocrine secretion. CR 1392 was also effective in reducing the elevated serum amylase activity, pancreatic weight, and histologic alterations even when administered after the pancreatitis had been induced.

Metiamide is an antagonist of histamine H2-receptors synthesized at Smith Kline & French Laboratories. It potently inhibited gastric acid secretion. Metiamide demonstrated promising clinical effects in patients with duodenal ulcers but questionable safety.

Trithiozine is an alkoxythiobenzamide said to have antisecretory and tranquillising properties without anticholinergic, antihistaminic, or ganglion-blocking effects. Trithiozine in animal studies proved to have a marked anti-secretory and anti-ulcer effect, along with a very low acute and chronic toxicity. Clinical trials with trithiozine have been performed in some European countries. The results of these trials, most of which were conducted on a double-blind basis, and including already several hundreds of patients, have shown that oral trithiozine: exerts a very significant action on both basal and stimulated gastric acid secretion, without a rebound hypersecretion; promotes, in most patients, a complete endoscopic healing of peptic ulcer, in addition to an early symptomatic relief; has a mild sedative action; does not affect the pancreatic secretion; is well tolerated even for long-term (up to 10 months) treatments.

Fluperamide was developed as an antiperistaltic agent for the treatment of diarrhea. However, information about the current use of the drug is not available.

Fosmenic acid was used for the treatment of atherosclerosis. Information about the current use of this drug is not available.

Sunagrel is a phenylethanolamine derivative patented by Maggioni Farmaceutici S.p.A. as platelet aggregation inhibitor and antilipidaemic agent.

Timofibrate is a thiazolidine derivative patented by Italchemi S.p.A.-Istituto Chimico Farmaceutico as antiatherosclerosis, anticholesteremic, and liver protecting agent.

Gemcabene calcium (PD 72953), the monocalcium salt of a dialkyl ether dicarboxylic acid, is a lipid-regulating compound that was first described in 1998. It down-regulates apolipoprotein C-III expression, enhancing the clearance of very low density lipoprotein (LDL), and reduces plasma triglycerides. It also raises high-density lipoprotein cholesterol (HDL). Unlike fibrates (blood trygliceride level lowering drugs), its mechanism of action is not linked to agonist or antagonist activity on PPAR-α receptors. There is limited information on the exact mechanism of action, but an anti-inflammatory profile was found, associated with a lowered expression of the high-sensitivity C-reactive protein gene regulating mechanisms. Gemcabene (administered as 6, 6’-oxybis [2, 2-dimethyl-4-hexanoic acid] monocalcium salt) has been investigated for treatment in a wide range of hyperlipidaemias, as well as atherosclerosis, and cardiovascular disorders. Gemcabene is generally well tolerated. One phase 2 study testing the preliminary efficacy and safety of gemcabene in children with established nonalcoholic fatty liver disease has been stopped early due to increasing weight and a rise in liver fat content in patients. Clinical trials are still ongoing.