Pridopidine is an experimental drug candidate belonging to a class of agents known as dopidines, which act as dopaminergic stabilizers in the central nervous system. As a dopamine stabilizer, pridopidine is thought to reduce the effects of dopamine when there’s too much and increase its effects when there’s too little. Pridopidine, therefore, plays two opposing roles in the brain, which stabilize dopamine levels. In this way, pridopidine is thought to help the brain reestablish a normal balance of neurotransmitters, and thus regain control over motion. Pridopidine intended to treat Huntington’s disease movement symptoms. Pridopidine was well tolerated and had an adverse event profile similar to a placebo.

Omtriptolide (previously known as PG490-88 or F60008), an immunosuppressant that has been shown to be the safe and potent antitumor agent and it has been approved entry into Phase I clinical trial for the treatment of prostate cancer in the USA. In addition, the drug is participating in phase I clinical trial for the treatment of myeloid leukemia. Experiments on animals have shown omtriptolide was highly effective in the prevention of murine graft-versus-host disease (GVHD). The immunosuppressive effect of the drug was mediated by inhibition of alloreactive T cell expansion through interleukin-2 production. However, this study was discontinued. Recently published article has shown omtriptolide possesses the potential as a prophylactic agent to prevent ischemia/reperfusion (I/R)-induced lung injury.

Lotrafiban (SmithKline Beecham) is a member of the latest generation of orally-active platelet GPIIb/IIIa blockers undergoing Phase III clinical trials to test the relative effectiveness versus other oral platelet inhibitors for ischaemic conditions including unstable angina, restenosis after PCI and stroke. Lotrafiban is converted from an esterified prodrug by plasma and liver esterases to a peptidomimetic of the arginine-glycine-aspartic acid amino acid sequence. This sequence itself mimics the binding site of fibrinogen and von Willebrand Factor to the platelet GPIIb/IIIa receptor. Preliminary results of the clinical trial APLAUD (antiplatelet useful dose) show that lotrafiban is clinically safe and well-tolerated in patients with recent myocardial infarction, unstable angina, transient ischaemic attack (TIA), or stroke when added to aspirin therapy. The Blockade of the IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial of SmithKline Beecham's oral GpIIb/IIIa blocker, lotrafiban, has been stopped early because of concerns about both safety and efficacy. The drug was showing a higher mortality rate than placebo, and was also associated with an increased incidence of serious thrombocytopenia and major bleeding. As a result of these findings the company has discontinued development of lotrafiban.

The novel compounds clamikalant (HMR 1883) or its sodium salt HMR 1098) have been shown to block selectively Kir6.2/SUR1-composed K(ATP) channels. Clamikalant is under development by Aventis Pharma (formerly Hoechst Marion Roussel) for the potential treatment of heart arrest and ventricular arrhythmias. Nevertheless, clamikalant and its sodium salt did not pass the clinical trials

LAMIFIBAN is a potent and selective nonpeptide glycoprotein IIb/IIIa antagonist. It inhibits platelet aggregation and thrombus formation by preventing the binding of fibrinogen to platelets. It was in clinical development as an injectable antithrombotic agent for treating and preventing acute coronary syndromes but showed no significant effects on clinical outcomes.

PF-03654746 is a potent, selective antagonist of the human H3 receptor, developed by Pfizer. It was in the clinical trial phase II for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy, Tourette syndrome as well as potential anti-allergy applications and in phase I of clinical trial for the treatment of Schizophrenia and Alzheimer's disease, but these investigations were discontinued.

Talnetant (SB-223412) is a selective, orally active neurokinin 3 receptor antagonist and is under development for the potential treatment of several disorders, including irritable bowel syndrome, schizophrenia, chronic obstructive pulmonary disease, cough, overactive bladder and urinary incontinence. The most common adverse effects were headache, fatigue, and nausea.

Ipazilide is an antiarrhythmic agent that prolongs ventricular refractoriness and possesses antiectopic activity. In clinical trials ipazilide administrations leads to dose- and time-dependent in decrease cardiac index and arterial pressure. Left ventricular filling pressure, right atrial pressure, and heart rate were not altered by ipazilide. Plasma concentrations of ipazilide peaked 90 minutes after administration of 100 or 200 of the drug, but peak concentrations were noted 3 hours after administration of 400 mg. The hemodynamic response correlated with the plasma concentration of ipazilide determined contemporaneously.

ICI-118551 is a selective β2 adrenergic receptor antagonist, that was originally developed for the regulation of blood pressure. ICI-118551 crosses the blood-brain barrier and it was in phase I clinical trials for the treatment of chronic anxiety. Currently, ICI-118,551 has no known therapeutic use in humans although it has been used widely in research to understand the action of the β2 adrenergic receptor, as few other specific antagonists for this receptor are known.

Saprisartan (formerly known as GR 138950) was developed as a potent long-lasting angiotensin II (AT1) receptor antagonist with high oral bioavailability. The drug was used for the treatment of hypertension and heart failure. However, these studies were discontinued.