Dexanabinol is the synthetic cannabinoid. It is inactive as a cannabimimetic, but exhibits pharmacological properties characteristic of an N-methyl-D-aspartate (NMDA)-receptor antagonist. It blocks NMDA-receptors stereospecifically by interacting with a site close to, but distinct from, that of uncompetitive NMDA-receptor antagonists and from the recognition sites of glutamate, glycine, and polyamines. This agent also scavenges peroxy radicals and protects neurons from the damages of reactive oxygen species. Furthermore, dexanabinol inhibits the activity of nuclear factor kappa B (NF-kB), thereby preventing the expression of NF-kB target genes, such as tumor necrosis factor alpha, cytokines and inducible nitric oxide synthase. Dexanabinol is a potent cerebroprotective agent, with a therapeutic window of about 4 h. Dexanabinol is safe, but is not efficacious in the treatment of traumatic brain injury. It was introduced into clinical trials for breast cancer and advanced solid tumors.

Fasitibant (MEN-16132) is a non-peptide sulfonamide-containing bradykinin hB2 receptor antagonist. It inhibits pro-inflammatory response in vitro and alleviates inflammatory hyperalgesia in rodent models of osteoarthritis. Menarini Group was developing fasitibant for the treatment of osteoarthritis. Fasitibant development has been discontinued.

Forasartan (also known as SC-52458) was developed as an orally active, competitive angiotensin (Ang) II subtype 1 (AT1)-receptor antagonist for the treatment of hypertension. Forasartan competes with angiotensin II for binding at the AT1 receptor subtype. It is known that angiotensin II is a vasoconstrictor and stimulates the synthesis and release of aldosterone, and blockage of its effects results in a decrease in systemic vascular resistance. Information about the further development of forasartan is not available.

Vanoxerine, also known as GBR-12909, is a piperazine derivative exhibiting potent selective inhibition of sodium-dependent dopamine reuptake transporters. Vanoxerine has been in clinical trials for Parkinsonism, depression and cocaine addiction but lacked efficacy. Vanoxerine has also been observed as a potent blocker of the following channels: cardiac hERG/IKr potassium channel, Calcium channel, voltage-dependent, L type, alpha 1C subunit (also known as Cav1.2) and voltage-gated sodium channel Nav 1.5. Vanoxerine was studied as a potential treatment for atrial fibrillation. However, phase III clinical trials for this condition were terminated because of cardiac safety concerns. Research also indicates that vanoxerine may have additional mechanisms of action including antagonist action at nicotinic acetylcholine receptors (nAChRs).

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.

Licostinel (ACEA 1021) is a potent competitive antagonist at the glycine site on the N-methyl-D-aspartate (NMDA) receptor. The robust efficacy of glycine/NMDA antagonists, such as ACEA 1021, in animal model of brain ischemia, together with good safety profile in animal models and in clinical trials, suggested that this class of NMDA antagonists should have good chance of success in the clinic as neuroprotectants. The clinical trial of ACEA 1021 for stroke was discontinued, mainly due to low solubility and lack of metabolism of the drug that led to the observation of crystals in the urine of some of the patients. In vivo ACEA 1021 reduced the rate of propagation of cortical spreading depression, an effect consistent with blockade of NMDA receptors. ACEA 1021 also decreased audiogenic myoclonus in resuscitated rats following cardiac arrest, and the minimum alveolar concentration for halothane, effects which suggest a reduction of excitatory amino acid neurotransmission. ACEA 1021 crosses the blood-brain barrier and blocks the pathophysiologic consequences of NMDA receptor overstimulation. It was neuroprotective with a favorable therapeutic window in models of transient and permanent cerebral ischemia, epilepsy and pain.

Metocinium iodide, a spasmolytic agent, is an antagonist of muscarinic acetylcholine receptors. The drug is used in patients with irritable bowel syndrome.

Lintitript (SR 27897) is a selective cholecystokinin type A (CCK-A) receptor antagonist, which was initially developed by Sanofi for appetite disorders. It is known, that CCK modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. Lintitript presumably alters feeding habits, however, the exact mechanism of action is not known. Lintitript was investigated in animals with anorexia nervosa, in addition, drug was in clinical trial for the patients with advanced pancreatic cancer, but these studies were discontinued.

Edonentan (BMS 207940) is a highly selective biphenylsulfonamide endothelin A receptor antagonist. (11)C- and (18)F-labeled analogs of edonentan were evaluated of novel PET radioligands for imaging the endothelin-A receptor. Edonentan was in clinical trials for the treatment of heart failure however its development has been discontinued.

Pelanserin is an antagonist of the serotonin 5-HT2 receptor and blocks alpha 1-adrenoceptor. Experiments on dogs have revealed that pelanserin showed adequate pharmacokinetic and pharmacodynamics profiles as an antihypertensive agent that is why the drug possessed potential therapeutic usefulness in the treatment of hypertension. Pelanserin was undergoing phase II clinical trials by Cinvestav in Mexico; however, these studied were discontinued.