Setastine (Loderix) is a potent antagonist of histamine H1-receptor mediated responses. Setastine inhibits anaphylactic shock in guinea-pigs sensitized by horse serum. No antiserotonin, anticholinergic and antiadrenergic effect of the compound can be detected. Setastine has a long lasting (up to 16 h) antihistamine effect with a good oral effectiveness. It shows no cardiovascular effects in cats. Setastine shows a much weaker CNS depressant activity than clemestine fumarate. In displacement studies (3H-mepyramine) setastine had significantly weaker affinity for the central nervous system (CNS) H1-receptors than clemastine fumarate. It is concluded that setastine is a non-sedative highly active H1-antagonist.

Nelivaptan is a selective, orally active, non-peptide vasopressin receptor antagonist selective for the V1B subtype. It showed promise in preclinical animal models and advanced to phase II clinical trials for the treatment of anxiety and depression; however, in 2008, Sanofi-Aventis announced that further development of this drug had been halted.

Ondelopran (also known as LY2196044) was developed as orally available opioid receptor antagonist for the treatment of alcoholism. This drug completed clinical trials phase III where was assess its efficacy and safety in the treatment of alcohol dependence in adult outpatients.

Pirenperone, a quinazoline derivative, is a selective antagonist at serotonin receptor 2A binding sites. The liposoluble compound pirenperone has been studied in a variety of behavioral tests including the sensitive d-lysergic acid diethylamide (LSD) cue discrimination assay, in which it served as a potent LSD-antagonist. Pirenperone also proved to be an effective antagonist of serotonin-mediated behavioral responses including the head twitch response thought to be mediated by serotonin receptors.

Odapipam is a benzazepine with high affinity and selectivity for D1-dopamine receptors. Labeled with C-11, it has been used as a PET radiotracer to visualize D1 receptors both in striatal and extrastriatal areas, such as the prefrontal cortex. Odapipam inhibits dopamine D1 receptor binding in vitro with low nanomolar to picomolar dissociation constants. The affinity of [11C]NNC 756 for D1 receptors is 0.18 nM. Odapipam was tested in phase I of clinical trials for the treatment of psychotic disorders, but failed.

Dexefaroxan is a selective alpha 2-adrenergic receptor antagonist. Вexefaroxan improved TgCRND8 (protein-transgenic mouse model of Alzheimer's disease) behavioral phenotypes and increased BDNF mRNA expression without affecting amyloid-β peptide levels. Dexefaroxan treatment also enhanced the number and complexity of the dendritic arborizations of polysialated neural cell adhesion molecule-positive neurons. The trophic effects of dexefaroxan on newborn cells might involve an increase in brain-derived neurotrophic factor, which was upregulated in afferent noradrenergic fiber projection areas and in neurons in the granule cell layer. By promoting the survival of new endogenously formed neurons, dexefaroxan treatment represents a potential therapeutic strategy for maintaining adult neurogenesis in neurodegenerative conditions, such as Alzheimer's disease, that affect the hippocampus. Dexefaroxan increases neuron survival in the olfactory bulb of the adult rat in vivo, putatively as a result of reducing the apoptotic fate of telencephalic stem cell progenies.

Declenperone is an antagonist of 5-HT2 receptors, developed by Janssen Pharmaceutica. The compound is claimed to have strong neuroleptic activity, as evidenced by experimental data obtained in apomorphine-tryptamine and norepinephrine test in rats, and the apomorphine test in dogs. Declenperone was used in a veterinary as a sedative.

Acolbifene, the active metabolite of EM-800, was identified as a pure antagonist that acts on both activation domains of the ERs. It is in Phase III clinical trials for the prevention of breast cancer and vasomotor symptoms (Hot flush) in postmenopausal women. Most commonly reported adverse events included irregular menses, leg/muscle cramps, diarrhea, and hot flashes. No serious adverse events were reported.

Milenperone, a dopamine receptor antagonist was studied as an antipsychotic drug. It participated in clinical trials in the management of aggressive behavior in alcoholics and epileptics. Besides, the effect of milenperone was studied for the aggressive behavior of oligophrenic patients. However, information about the further development of the drug is not available.