Elarofiban is a novel nonpeptide glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist. It inhibits thrombin-induced platelet aggregation in human gel-filtered platelets and platelet aggregation in human platelet-rich plasma (PRP) in response to collagen, arachidonic acid, ADP, and SFLLRN-NH(2). Elarofiban had adequate oral pharmacokinetics in dogs and excellent oral pharmacodynamics. Elarofiban has been in phase II clinical trials for the treatment of myocardial infarction and thrombosis. However, this research has been discontinued.

Draflazine is a member of the lidoflazine. Draflazine is a potent inhibitor of equilibrative nucleoside transporters (ENTs). It is more selective for ENT1 relative to ENT2. Draflazine is cardioprotective due to potentiation of receptor-mediated effects of adenosine in the ischemic myocardium. It has also been tested for enhancing cardiac functionality in isolated hearts during storage or transport for transplant operations. Draflazine exhibits overactive bladder activity. It is not yet approved for clinical use.

Mobecarb is morpholineacetic acid derivative patented by Carlo Erba Societa per Azioni to prevent vascular rupture among persons afflicted with arterial hypertension. In preclinical models Mobecarb shows the capillary protective activity in partially omentectomized rats.

Trifenagrel is a potent inhibitor of arachidonate (AA)- and collagen-induced aggregation of platelets from several animal species and humans. When trifenagrel was administered p.o. to guinea pigs, there was a sustained (greater than 3 hr) inhibition of AA- and collagen-induced platelet aggregation ex vivo. In humans, trifenagrel inhibited the second phase of ADP-induced aggregation ex vivo up to 6 hr after a single dose of 100 to 300 mg p.o. The mechanism of action of trifenagrel appears to be a reversible inhibition of platelet AA cyclooxygenase. Although trifenagrel caused gastrointestinal irritation in dogs and humans, the nature of the damage suggests that the compound may have acted as a local irritant in these species. Furthermore, compared to aspirin trifenagrel produced significantly less gastric irritation and fecal blood loss in humans. Trifenagrel was developed for the treatment of ischemic heart disorders. However, this development was discontinued.

Rolafagrel (FCE 22178) is a selective thromboxane synthase inhibitor that has been evaluated for use in the treatment of diabetic nephropathy and thrombosis. Rolafagrel inhibits platelet and glomerular thromoxane synthase in animal and human kidney disease. A phase I clinical trial did not report drug-related adverse events. No information is available on current use of rolafagrel.

Tulopafant [RP 59227] is a platelet-activating factor (PAF) antagonist which was being developed by Rhône-Poulenc Rorer as an antiasthmatic agent. Double-blind, placebo-controlled clinicacl trial showed that RP 59227 attenuated the release of NCA and ECA after antigen challenge, and reduced the effect of exogenously added PAF in inducing eosinophil chemotaxis but did not protect against the antigen-induced early or late phase response in asthmatics. RP 59227 has also been shown to effectively reduce myocardial infarct size and the incidence of ischemia and reperfusion-induced arrhythmias in barbital-anesthetized dogs. Development of Tulopafant for asthma treatment has been discontinued.

Sulotroban is a phenoxyalkylcarboxylic acid derivative patented by Boehringer Mannheim G.m.b.H. as thrombocyte aggregation inhibitor and lipid-lowering agent. Sulotroban is the first thromboxane A2 receptor antagonist available for use in man. Its antagonistic profile appeared to be specific and competitive both for platelets and vascular or bronchial smooth muscle receptors. In preclinical models Administered as a single dose of 800 mg, sulotroban antagonized arachidonic acid-induced, collagen-induced, and U-46619-induced platelet aggregation. In clinical trials, Sulotroban shows superior efficacy to placebo in preventing acute problems during, or restenosis after, coronary angioplasty. Chronic dosage with the drug did not lead to any accumulation of its blocking effect on platelet function; the effect of each dose declined to zero 6-7 hours after dosing.

Bemitradine (SC-33643), a diuretic antihypertensive agent that was dropped from the development. Experiments on rodents have revealed this drug was a carcinogen and acted by a hormonally modulated promotional activity in inducing tumors in the liver and mammary glands.

Tizolemide is a sulphonamide diuretic. The effect on transepithelial Na transport of tizolemide was investigated in isolated frog skin (Rana temporaria). It was found that tizolemide (2-5 mM, serosal side) decreased transepithelial Na transport (measured as short circuit current and as net sodium flux) within 60 min to 25-40% of the control level resulting from reduction of the unidirectional sodium influx. Tizolemide has alkaline properties and is cleared by a tubular transport system which differs from the PAH-excreting system which transports thiazide diuretics. Tizolemide was almost completely absorbed from the gastrointestinal tract. The drug was mainly eliminated via tubular secretion. Renal clearance of the drug was much lower in patients with compensated cardiac failure than in healthy subjects because of low renal plasma flow. As a consequence, plasma half-life was prolonged considerably in some patients. It was concluded that drugs with mainly tubular renal elimination may have a reduced elimination rate in patients with cardiac diseases despite normal glomerular filtration rate.