Befetupitant (Ro67-5930) is a high-affinity, competitive, tachykinin 1 receptor (NK1R) antagonist that was initially invented by Hoffmann-La Roche as a potential antiemetic drug. These studies were discontinued, because of the clinical trials with the more suitable drug, netupitant. Befetupitant was also investigated for topical application to reduced corneal neovascularization in the alkali burn model. However, the drug was toxic and was not tested in the suture model.

Idronoxil (Phenoxodiol) is a synthetic flavonoid derivative developed by MEI Pharma for cancer treatment. Idronoxil inhibits proliferation of many cancer cell lines and induces apoptosis by disrupting FLICE-inhibitory protein, FLIP, expression and by caspase-dependent and -independent degradation of the X-linked inhibitor of apoptosis, XIAP. In addition, Idronoxil sensitizes drug-resistant tumour cells to anticancer drugs including paclitaxel, carboplatin, and gemcitabine. The antiproliferative effects of Idronoxil are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells. Idronoxil displays anti-cancer activity against all forms of cancer tested in vitro and in vivo to date, using cells representative of all major forms of cancer. While having a modest ability to kill cancer cells(IC50 range between about 1-5 uM), preclinical studies point to its optimal use being to sensitize cancer cells to the toxic effects of standard therapies (chemotherapy and radiotherapy). The rationale is that a sub-lethal inhibitory effect on sphingosine kinase activity reduces the ability of the cancer cell to operate drug-resistance mechanisms and to effect repair of drug- or radiation-induced damage to DNA. In the case of cytotoxic drugs such as cisplatin, carboplatin, paclitaxel, Doxorubicin, and gemcitabine, Idronoxil is an exquisite sensitizer, increasing the cytotoxic potential of those agents by between 103 -105 times, in the process restoring sensitivity to cancer cells highly refractory to those agents.

Isamoltan (CGP 361A) is a β-adrenoceptor and serotonin 1B receptor antagonist. Isamoltane has reported activity as an anxiolytic in man. Isamoltan had been in phase III clinical trials for the treatment of anxiety. However, this research has been discontinued.

GV 150526A (gavestinel) is an investigational drug for a neuroprotective therapy of acute ischemic stroke within 6 hours of symptom onset. It is a potent and selective non-competitive antagonist at the glycine site of the N-methyl-D-aspartate receptor (NMDA) which reduces infarct volume in experimental stroke models. Gavestinel acts at the strychnine-insensitive glycine binding site of the NMDA receptor-channel complex with nanomolar affinity (pKi = 8.5), coupled with high glutamate receptor selectivity. Gavestinel displays higher than 1000-fold selectivity over NMDA, AMPA and kainate binding sites and is orally bioavailable and active in vivo. GV 150526A inhibited convulsions induced by NMDA in mice, when administered by both IV and po routes (ED50 = 0.06 and 6 mg/kg, respectively). The safety and efficacy of GV150526 were studied in two phase III randomized placebo-controlled clinical trials of acute ischemic stroke patients within 6 h from onset [The Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas Trials] sponsored by GlaxoSmithKline. The results of these trials suggested that gavestinel was not of substantial benefit or harm to patients with primary intracerebral hemorrhage.

Mifentidine, a histamine H2 receptor antagonist, was studied to treat the duodenal ulcer. This drug was in phase II clinical trials when apparently further researches had been discontinued.

Picartamide had potent antisecretory and antiulcerogenic effects which were, at least, 10 times more pronounced than those of cimetidine. The mechanism of action of picartamide has not yet been determined but it seems that an anticholinergic or an H2 receptor antagonist effect should be excluded. The results show that picartamide is also active on the pure vagus-stimulated gastric acid secretion. The lack of effect upon gastric pepsin and plasma PP suggests that picartamide is not likely to act on the basolateral cholinergic receptor and that it affects further cellular steps involved in hydrogen ion secretion.

Tecarfarin (also known as ATI-5923), an anticoagulant, is a vitamin K reductase antagonist. Tecarfarin is participating in phase III clinical trials for the treatment of thromboembolism and thrombosis. On March 11, 2019, Espero BioPharma Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for tecarfarin for the prevention of systemic thromboembolism of cardiac origin. Tecarfarin is metabolized by esterases, escaping metabolism by the cytochrome P450 system and thereby avoiding cytochrome P450-mediated drug-drug or drug-food interactions as well as genetic variations found in the cytochrome P450 system.

Idalopirdine (Lu AE58054) is a Serotonin 6 receptor (5-HT6) antagonist. Idalopirdine exrets good oral bioavailability and robust efficacy in a rat model of cognitive impairment in schizophrenia. In rats idalopirdine potentiates the effects of acetylcholinesterase inhibitor donepezil on two pharmacodynamic biomarkers associated with cognition, i.e. neuronal oscillations and extracellular ACh levels in the hippocampus. Such potentiation could contribute to the procognitive effects of idalopirdine observed in donepezil-treated Alzheimer's disease patients. The compound is being developed by Lundbeck as an adjunctive therapy with acetylcholinesterase inhibitor donepezil, and is in phase III development for the treatment of Alzheimer's disease in multiple countries worldwide. A phase II trial for the treatment of cognitive impairment associated with schizophrenia was conducted; however no recent reports of development for idalopirdine have been identified.

(R)-(+)-Propranolol (also known as DEXPROPRANOLOL) is the less active enantiomer of propranolol and is an antagonist of the beta-adrenergic receptor. It is known, that propranolol had been used for myocardial infarction; arrhythmia, anxiety and some other disease, but adverse effects instigated the replacement by newer drugs.

SR 202 is an antagonist of peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity induced by troglitazone but not of basal PPARγ activity. It is selective for PPARγ, not affecting basal or agonist-induced transcriptional activity of PPARα, PPARβ, or the farnesoid X receptor (FXR). It inhibits PPARγ-dependent differentiation of preadipocyte 3T3-L1 cells in a dose-dependent manner. SR 202 (400 mg/kg) decreases the amount of weight gained and white adipose tissue mass accumulated by mice fed a standard or high-fat diet for ten weeks and is associated with lower PPARγ mRNA levels. It protects against high-fat diet-induced insulin resistance in wild-type mice and improves insulin sensitivity in ob/ob mice.