Bitopertin is a Glycine transporter type 1 inhibitor which was developed by Hoffmann-La Roche for the treatment of patients with schizophrenia. The drug was shown to be potent in vitro, however it failed to meet primary endpoints in phase III. Bitopertin was also tested for the treatment of obsessive-compulsive disorder, but the development stopped in phase II.

Synthetic compound Erteberel (LY500307) is a highly potent and selective ERβ agonist; it has a 12-fold higher affinity for ERβ than ERα and exhibits 32-fold more functional potency. LY500307 was well tolerated in benign prostatic hypertrophy (BPH) patients with no side effects and it is currently being tested in phase 2 clinical trials for improving negative symptoms and cognitive impairment associated with Schizophrenia. In BPH clinical trial incidence of adverse events was comparable between treatment groups, and no clinically meaningful changes in laboratory tests were observed.

LY404039 [(-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid] is an agonist of orthosteric metabotropic glutamate receptor (mGluR)2/3. In addition, it acts as an agonist at dopamine D2 receptors. LY404039 demonstrated broad antipsychotic and anxiolytic efficacy across multiple animal models. LY-2140023 is a methionine amide prodrug of LY-404039 being developed by Eli Lilly & Co for the potential oral treatment of schizophrenia.

Volinanserin (MDL-100,907) is a highly selective 5-HT2A receptor antagonist. It is widely used in scientific research to investigate the function of the 5-HT2A receptor. Volinanserin is also being trialed as a potential antipsychotic, antidepressant and treatment for insomnia. Volinanserin (M-100907) was in phase III trials for chronic schizophrenia. In August 1999, development was discontinued for acute schizophrenia (schizoaffective disorder) on the basis of poor results. M-100907 is also active in animal models involving blockade of NMDA glutamatergic channel receptors, an effect known to resemble some behavioral symptoms of schizophrenia in man. M-100907 is also claimed in other patents for the treatment of thromboembolic disorders, for the treatment of various developmental neurological disorders such as autism and attention deficit hyperactivity disorder.

Bifeprunox, code name DU-127,090 is an atypical antipsychotic agent, which combines minimal D2 receptor agonism with 5-HT receptor agonism. Bifeprunox was in phase III of clinical trials for the treatment of schizophrenia, Bipolar Depression and in phase I for Parkinson's disease, but these studies were discontinued because efficacy data did not support pursuing the existing development strategy of stabilization of non-acute patients with schizophrenia.

Pridopidine is an experimental drug candidate belonging to a class of agents known as dopidines, which act as dopaminergic stabilizers in the central nervous system. As a dopamine stabilizer, pridopidine is thought to reduce the effects of dopamine when there’s too much and increase its effects when there’s too little. Pridopidine, therefore, plays two opposing roles in the brain, which stabilize dopamine levels. In this way, pridopidine is thought to help the brain reestablish a normal balance of neurotransmitters, and thus regain control over motion. Pridopidine intended to treat Huntington’s disease movement symptoms. Pridopidine was well tolerated and had an adverse event profile similar to a placebo.

Fluperlapine is dibenzazepine chemically and pharmacologically similar to clozapine. Fluperlapine had no cataleptogenic effect and did not inhibit the apomorphine- and d-amphetamine-induced stereotypes. Fluperlapine is fairly effective neuroleptic drug with a fast-acting antipsychotic affect. The effects in movement disorders imply that fluperlapine is less liable than traditional neuroleptics to induce acute extrapyramidal side effects and tardive dyskinesia and is particularly beneficial in the treatment of patients vulnerable to neurological side-effects. It was demonstrated efficacy in the treatment of a variety of medical conditions including schizophrenia, psychosis associated with Parkinson's disease and dystonia. It has the capacity for producing life-threatening agranulocytosis.

MK-0557, trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro [6 azaisobenzofuran-1(3H),10-cyclohexane]-40-carboxamide, is an orally available Neuropeptide Y (NPY5) receptor antagonist. MK-0557 was studied in the clinical trials for the treatment of obesity, however, MK-0557 did not significantly increase the weight loss efficacy. MK-0557 safety and effectiveness were studied in a trial for the treatment of cognitive impairment in patients with schizophrenia. It seems MK-0557 development was discontinued.

Clorotepine (aka octoclothepin or octoclothepine) is an antipsychotic from the tricyclic group derived from perathiepin. It was originally developed in 1965 and marketed in the Czech Republic by Spofa in or around 1971 for the treatment of schizophrenic psychosis. Clorotepine has a high affinity for the dopamine (D1, D2, D3, D4), receptors the serotonin 5-HT (2A, 2B, 2C, 6, 7) receptors, the alpha-adrenergic receptors (1A, 1B, 1D), and the histamine H1 receptors. In most instances, it acts as an antagonist (or inverse agonist). Clorotepine will also block the reuptake of norepinephrine by inhibiting the norepinephrine transporter.

Org 25935 (SCH 900435) is a synthetic drug developed by Organon International, which acts as a selective inhibitor of the glycine transporter GlyT-1. In human trial for prevention of relapse in alcohol-dependent patients in Org 25935 demonstrated no benefit over placebo in preventing alcohol relapse. Org 25935 was tested as an adjunctive treatment to atypical antipsychotics in predominant persistent negative symptoms of schizophrenia, where it did not differ significantly from placebo in reducing negative symptoms or improving cognitive functioning. Clinical trials against panic disorder did not show any benefit compared to placebo.