Gadopenamide is an MRI contrast agent that was introduced in 1991. It has been investigated as a potential clinical contrast medium by Schering AG (Germany), but has never been used as such.

Tisoquone is the hypolipaemic agent.

Butobendine is trihydroxybenzoic acid derivative with marked antiarrhythmic activities in rats and cats.

Temelastine (also known as SK&F 93944) is a competitive histamine H1-receptor antagonist, which does not penetrate the central nervous system. This drug was studied as an anti-allergic agent. Experiments on animals have shown that the drug was efficacious vs. pharmacologic and antigen-induced bronchoconstriction.

Pirifibrate is a fibric acid derivative. Pirifibrate was used in the treatment of hyperlipoproteinemia (HLP). After treatment with pirifibrate, mean plasma levels of cholesterol fell about 20% in types IIa and IIb HLP; triglycerides fell between 30% and 46% in types IIb and IV HLP. Slight increases in alpha-lipoproteins in the three types of HLP were measured. Prebeta-lipoprotein levels fell considerably in types IIb and IV. The variations observed in beta-lipoprotein levels were significant only in type IV, which initially showed low values.

Piclidenoson (CF101), generically known as IB-MECA (methyl 1-[N6-(3-iodobenzyl)-adenin-9-yl]-b-D-ribofuronamide), is an oral small molecule drug formulated in a tablet. The activity of CF101 as an anti-inflammatory agent has been tested in a number of different experimental models including adjuvant and collagen induced arthritis and inflammatory bowel disease. CF101 is a highly specific agonist at the A3AR known to induce a robust anti-inflammatory effect in different experimental animal models. The CF101 mechanism of action entails down-regulation of the NF-κB-TNF-α signaling pathway, resulting in inhibition of pro-inflammatory cytokine production and apoptosis of inflammatory cells. Piclidenoson is currently being developed for the treatment of autoimmune inflammatory diseases like RA and psoriasis, hoping to replace the current standard of care, methotrexate (MTX). Can-Fite has tested CF101 in a number of Phase II studies in different diseases. A Phase II study in Psoriasis successfully met its primary endpoint showing that CF101 effectively ameliorated disease symptoms. In an interim analysis of the Phase II/III study the data justified full enrollment of the study. Phase II studies in Rheumatoid Arthritis (RA) demonstrated efficacy of CF101 given as a monotherapy. Moreover, a direct correlation between A3AR at baseline and patients’ response to CF101, suggesting its utilization as a predictive biomarker. Piclidenoson is headed into Phase 3 trials for RA and psoriasis.

Silicristin is a flavonolignan isolated from Silybum marianum and has been shown to exhibit inhibitory activities against lipoxygenase and prostaglandin synthetase. It has a role as a radical scavenger, a lipoxygenase inhibitor, a prostaglandin antagonist and a metabolite. It is a flavonolignan, a member of 1-benzofurans, a polyphenol, an aromatic ether and a secondary alpha-hydroxy ketone. Silicristin is a potent inhibitor of the thyroid hormone transporter MCT8. Silicristin is a sodium pump inhibitor, it inhibited Na(+)/K(+)-ATPase (NKA) with IC50 of 110 uM. Silicristin exhibits relatively good antioxidant effectiveness against phenylglyoxylic ketyl radicals and DPPH. Silicristin protects cardiomyocytes against doxorubicin-induced oxidative stress is due mainly to their cell membrane stabilization effect, radical scavenging and iron chelating potency.

Etintidine is a potent competitive antagonist of histamine H2-receptors. It has a low level of antiandrogenic activity. Etintidine was being investigated in the treatment of peptic ulcer, however, its development has been discontinued.

Noberastine (NOB), a histamine H1 antagonist, has potent and specific peripheral antihistaminic activity. Noberastine, a furan derivative of nor-astemizole (an astemizole metabolite), has been shown to have a more rapid onset, and shorter duration of action than astemizole with peak antihistaminic activity at 4h following ingestion. Noberastine is rapidly absorbed and the peak plasma levels are obtained within 2 h of oral dosing. In preclinical studies Noberastine has been shown to lack central nervous system effects. After subacute (steady-state) administration of noberastine, there was increasing inhibition of weal and flare formation with higher doses of the drug. The 30 mg daily dose showed maximum antihistaminic effects.

Bromadoline is a selective agonist of a μ-opioid receptor with potent analgesic activity developed by the Upjohn company in the 1970s for pain management.