Timegadine Is a quinolylguanidine derivative patented by Loevens Kemiske Fabrik Produktionsaktieselskab as an anti-arthritic agent. Timegadine acts as a potent, competitive inhibitor of cyclo-oxygenase and lipo-oxygenase. Timegadine significantly inhibits both the primary and secondary lesions of rats adjuvant arthritis when the treatment is initiated on the day of the disease induction and continues for 28 days. Timegadine is able specifically to prevent the development of the swelling of the non-injected paw until 28 days after the adjuvant injection when administered for 5 days prior to and 5 days after the induction of the disease, in analogy with the effect of cyclophosphamide. In clinical trials, Timegadine significantly improves both biochemical and clinical markers of disease activity, i.e. ESR, serum IgG and IgM, leukocyte and platelet counts, duration of morning stiffness, Ritchie index, number of swollen joints and pain. Timegadine treatment associated with gastrointestinal and allergic side effects.

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.

MK 0777 is a selective GABAA α2/3 receptor partial agonist, for potential use in the treatment of Schizophrenia, Anxiety Disorder, and Generalized Anxiety Disorder. MK-0777 is functionally selective for the α2 and α3 subunits, with virtually no activity for the α1 and α5 subunits. Therefore, MK-0777 cause less sedation, interact less with alcohol, and exhibit less abuse potential and physical dependence than benzodiazepines. Unfortunately, in clinical trials, MK-0777 has little benefit for cognitive impairments in people with schizophrenia and anxiety disorder.

Seletracetam, a pyrrolidone derivative is a new drug in epilepsy development. Seletracetam has high binding affinity to the synaptic vesicle 2A (SV2A) protein. In addition, was discovered, that the drug bound to N-type calcium channels and inhibited high-voltage-activated Ca2+ currents and intracellular Ca2+ increase. Seletracetam participated in Phase III clinical trials; however, all these studies for the treatment of epilepsy were terminated. Moreover, it is unknown whether planned phase IIb/III trials will begin.

Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine occurs widely in plants and animals, and is metabolized by the enzyme monoamine oxidase. Tyramine is an alpha-adrenergic agonist. Hypertension can occur, from ingestion of tyramine-rich foods in conjunction with monoamine oxidase inhibitors. The possibility that tyramine acts directly as a neurotransmitter was revealed by the discovery of a G protein-coupled receptor with high affinity for tyramine, called TAAR. It exhibits sympathomimetic effects by causing the release of endogenic norepinephrine. It has been used in mydriatic eyedrops. This has been said to reduce the intraocular pressure in rabbits and in some patients with open-angle glaucoma.

Milacemide, a prodrug for glycine, is an inhibitor of the B form of monoamine oxidase. This drug could enhance dopaminergic activity in the brain and could be used as therapy for Parkinson's disease. Milacemide participated in clinical trials as a treatment for senile dementia of the Alzheimer type (SDAT). However, results have shown the drug was not an effective treatment in enhancing cognition in SDAT patients. In addition, milacemide has been tested for antiepileptic efficacy; however, this study was discontinued.

Antineoplaston A10 is a piperidinedione antineoplaston with potential antineoplastic activity. Antineoplaston A10 was originally isolated from human urine but is now synthetically derived. This agent intercalates into DNA, resulting in cell cycle arrest in G1 phase, reduction of mitosis, and decreased protein synthesis. Antineoplaston A10 may also inhibit ras-oncogene expression and activate tumor suppressor gene p53, leading to cell differentiation and apoptosis. Antineoplaston A10 has been used in trials studying the treatment of glioma, sarcoma, lymphoma, lung cancer, liver cancer, and kidney cancer, among others.

UK-390957 is a selective serotonin reuptake inhibitor (SSRI) that was in phase II/III development in the USA, European Union and other territories with Pfizer, for the treatment of Premature ejaculation. UK-390957 represented a major development in sexual medicine, and offered patients the convenience of on-demand dosing, significant improvements in IELT, ejaculatory control, and sexual satisfaction with minimal adverse effects. However development of UK-390957 was discontinued.