Apratastat (Tmi 005) was developed by Wyeth Research as a dual TNF-alpha-converting enzyme and matrix metalloprotease-13 inhibitor for the treatment of rheumatoid arthritis. Apratastat was in phase II clinical trials, but because of the lack of efficacy, this trial was terminated.

Ridazolol is a cardioselective and vasodilating beta-adrenergic receptor antagonist. It also has moderate alpha-adrenolytic activity (the presence of a heterogeneous population of postjunctional alpha adrenoceptors has been suggested). Ridazolol was investigated for use in arrhythmias and ischaemic heart disorders. In patients with confirmed coronary artery disease and reproducible ST-segment depression, blood pressure and heart rate under exercise were significantly reduced for 5 hours, and improvement of ST-segment depression lasted 1 hour. Ridazolol is well tolerated. This drug is not currently used.

Rolgamidine is an antidiarrheal agent. No information on current use of this compound is available.

Eprodisate (1,3-propanedisulfonate) is a negatively charged, sulfonated molecule of low molecular weight that has structural similarities to heparin sulfate; it is a glycosaminoglycan mimetic that binds to the glycosaminoglycan (GAG) binding site on serum A amyloid (AA) to prevent its interaction with glycosaminoglycan and arrest amyloidosis, or inhibit amyloid deposition. In nonclinical toxicity studies in two animal species (i.e., rat and dog), eprodisate was administered orally at doses of up to 2000 mg/kg/day for 39 weeks: eprodisate showed low toxicity potential at doses several fold higher than the anticipated clinical dose, was well tolerated upon chronic exposure and was found to be nonmutagenic and nonclastogenic. Furthermore, a series of safety pharmacology studies showed that eprodisate does not have any clinically significant effect on major organ function.

Spiroxatrine is a drug which acts as a selective antagonist at both the 5-HT1A receptor and the α2 adrenergic receptor. Spiroxatrine was identified as a moderately potent but non-selective agonist at the human nociceptin/orphanin FQ receptor, ORL1

Teclothiazide is a thiazide diuretic that has never been marketed. Information about the current use of this drug is not available.

Vestipitant, also known as GW597599, is a neurokinin1 receptor antagonist that was being developed by GlaxoSmithKline for the treatment of postoperative nausea and vomiting. Vestipitant is one of the most potent and selective NK(1) receptor antagonists ever discovered, showing appropriate pharmacokinetic properties and in vivo activity. Its actions support the utility of NK(1) receptor blockade in the alleviation of anxiety and, possibly, depression. It was under development as a potential antiemetic and anxiolytic drug, and as a treatment for tinnitus and insomnia. Vestipitant was shown to improve sleep maintenance in patients with primary insomnia, with no associated next-day cognitive impairment. The effects on wake after sleep onset and total sleep time were maintained following repeated dosing. Vestipitant has anxiolytic properties and a good safety profile. Vestipitant was investigated for potential effect against chronic tinnitus as a stand-alone treatment and in conjunction with a selective serotonin reuptake inhibitor, paroxetine. Although well-tolerated vestipitant, alone or in combination with paroxetine, was not effective in ameliorating tinnitus in this patient group.

Minocromil was studied as a histamine receptor antagonist for the treatment of asthma. However, further development of the drug was discontinued.

Pivenfrine is a sympathomimetic agent. Pivenfrine is an analog of phenylephrine hydrochloride (PE) ten times more potent as a mydriatic. It is a product of the esterification of a molecule of pivalic acid (PA) to the p-hydroxyl group of PE. It is, therefore, more lipophilic than PE is, and penetrates the cornea more readily. Pivenfrine is called a prodrug of PE because it is enzymatically hydrolyzed to the active, parent compound (PE), and to PA, before reaching its desired active site in the eye. The pivenfrine-treated corneas without epithelium significantly increased in thickness, whereas no change in thickness was observed in corneas with epithelium intact.

Siguazodan is a selective inhibitor of phosphodiesterase 3. It caused significant increases in cardiac output and stroke volume. It is orally active inotropic/vasodilator agent with a sustained duration in vivo. Siguazodan has potential utility in the treatment of congestive heart failure. Siguazodan has anti-platelet actions over the same concentration range that it is an inotrope and vasodilator. Siguazodan caused bronchodilation. In combination with phosphodiesterase 4, it may be useful in the therapy of asthma.