Piflutixol is a thioxanthene neuroleptic which combines a very potent dopamine antagonistic effect with a potent effect in tests for sedative properties. It was found to have a very strong antagonistic effect against stereotypies induced by dopamine agonists in mice, rats and dogs as well as against apomorphine induced vomiting in dogs. This indicates that piflutixol must be considered as one of the most potent dopamine receptor blocking agents. Piflutixol seems to be the hitherto most potent inhibitor of dopamine-stimulated adenylate cyclase. There was a linear relationship between D-1 dopamine receptor occupation by [3H]piflutixol and inhibition of dopamine sensitive adenylate cyclase. Piflutixol markedly antagonizes the effect of noradrenaline, 5-HT and to some extent histamine, whereas the affinity for muscarinic receptors was rather weak. Piflutixol has a high affinity for dopamine structures within the brain. It is a compound with a very long duration of action.

CPI-1189 is a synthetic benzamide with antioxidant properties that blocks tumor necrosis factor-alpha (TNFalpha) effects in animal models. It has neuroprotective properties in model systems for HIV-associated neurotoxicity and thus is a candidate for neuroprotective therapy in humans with HIV-associated CNS disease. CPI-1189 was at the phase II stage of clinical development for the treatment of dementia associated with Parkinson's disease and AIDS Dementia Complex, however, development has been discontinued.

R-etodolac (SDX-101) is the non-cyclooxygenase 2-inhibiting R-enantiomer of the non-steroid anti-inflammatory drug etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid). The absolute configuration of the enantiomer is R-(-)-etodolac. R-etodolac specifically bound retinoid X receptor (RXRalpha), inhibited RXRalpha transcriptional activity, and induced its degradation by a ubiquitin and proteasome-dependent pathway. In addition R-etodolac can disrupt the beta-catenin signaling pathway. R-etodolac exerts antineoplastic properties. R-etodolac was in phase 2 studies for the treatment of hematologic malignancies however development was discontinued.

Cobristone is a locally acting chloride channel activator that works to stimulate and protect the mucosal barrier function. Cobristone is being developed by the Sucampo Pharmaceuticals, Inc. for the prevention of oral mucositis and for the treatment of non-erosive reflux disease (NERD), a major subtype of gastroesophageal reflux disease. The development of the drug was terminated after phase 2 clinical trials failed to meet its primary endpoints.

Treptilamine is a spasmolytic and anticholinergic agent. In the pilot study systolic blood pressure in volunteers decreased significantly 5 to 15 min after intravenous application of the substance for 5 or 30 min. No alteration of circulation was observed after oral application at any dose. All volunteers felt tired. A significant decrease of systolic blood pressure (15 mmHg for 10 min immediately after application) occurred after 15 mg of substance were applied intravenous in the double-blind study. Two of five volunteers recorded a burning sensation in the venous wall which was followed by drowsiness. One volunteer felt increasingly tired after oral application. No influence of the substance could be seen on the clinicochemical parameters examined. The drug treptilamine hydrochloride changes the diameter of the pupils.

Bisdemethoxycurcumin (BDMC) is a minor constituent (approximately 3%) of curcuminoids that has been shown to be more stable than the other two main curcuminoids, that is, curcumin and desmethoxycurcumin. Bisdemethoxycurcumin inhibits the proliferation and survival of several types of tumor cells including colon cancer cells, breast cancer cells, leukemia cells, and glioma cells. In addition, Bisdemethoxycurcumin suppresses cancer invasion and has the highest anti-metastatic potency in HT1080 human fibrosarcoma cells among the three curcuminoids. Bisdemethoxycurcumin has been reported to possess anti-oxidant and anti-inflammatory activities. However, the underlying molecular mechanisms responsible for the inhibitory action of Bisdemethoxycurcumin on tumor invasion and migration have remained largely unknown. More interestingly, the anti-cancer effects of Bisdemethoxycurcumin are comparable to and sometimes more potent than those of curcumin in different conditions.

Fluoromisonidazole F-18 ([F-18] FMISO) is used as a positron emission tomography (PET) radiotracer for imaging. It is generated by labeling fluoromisonidazole with fluorine-18. It is the most widely used nitroimidazole imaging agent for use as a non-invasive way to localize and quantify hypoxia. [18F] decays by positron emission. FMISO binds covalently to cellular molecules at rates that are inversely proportional to intracellular oxygen concentration. In hypoxic cells, FMISO is trapped, which is the basis for the use of this tracer to measure hypoxia.

Duazomycin (N-acetyl-DON) is one of the few naturally occurring compounds containing an aliphatic alpha diazoketo group, and is produced by Streptomyces ambofaciens. It is a derivative of 6-diazo-5-oxo-L-norleucine (DON) which was initially isolated from an unidentified Streptomyces species and which is produced together with N-acetyl-DON and duazomycin B (azotomycin) by S. ambofaciens. Duazomycin inhibited purine biosynthesis and caused accumulation of phosphoribosyl-N-formylglycineamide (FGAR) at low levels of inhibitor; higher levels blocked the synthesis of FGAR, indicating that the antibiotic behaved essentially like DON. Duazomycin is readily deacetylated by mammalian acylase to DON. As a glutamine antagonist, duazomycin was used in combination with azathioprine for the treatment of patients with advanced Wegener’s granulomatosis with renal involvement. Prolonged survival, remission of systemic signs and symptoms, roentogenologic improvement of pulmonary lesions, reduction in proteinuria and arrest of progression of renal insufficiency were observed.

16alpha-Bromoepiandrosterone (HE2000) is a synthetic steroid that limits non-productive inflammation, enhances protective immunity and improves survival in clinical studies of patients with human immunodeficiency virus (HIV), malaria and tuberculosis infections. HE 2000 had also shown activity in vitro against cytomegalovirus, polio, hepatitis B and C and influenza virus. 16alpha-Bromoepiandrosterone inhibits glucose-6-phosphate dehydrogenase (G6PD) and cell proliferation. HE 2000 was in phase II development for the Hepatitis B in Malaysia and Singapore, but it was suspended.