Cinuperone is an antagonist of D2, alpha1 adrenergic and sigma receptors. The drug selectively inhibits dopamine agonists-dependent behaviors, mediated by the limbic system. The clinical development of the drug as an antipsychotic was terminated due to orthostasis.

(+)-SKF-10,047 is a sigma-opioid receptor agonist. (+)-SKF-10,047 is distinct from its (-)-enantiomer in binding pattern and associated behavioural effects. (+)-SKF-10,047 stress-induced motor suppression, while its (-)-optical isomer was inactive. Besides activation of sigma-1 receptor, (+)-SKF-10,047 is inhibitor of Na(V)1.2 and Na(V)1.4 channels.

PD 144418 oxalate is a remarkably potent and selective sigma1 receptor ligand having potential antipsychotic properties. PD 144418 oxalate displayed an apparent affinity (Ki) of 0.08 nM for sigma1 sites in guinea pig brain membranes and a Ki of 1377 nM for sigma2 sites in rodent neuronal NG108-15 cell membranes. PD 144418 oxalate was classified as sigma1 receptor antagonist based upon several assays, including the ability to attenuate mescaline-induced scratching in mice. PD 144418 oxalate attenuates cocaine-induced hyperactivity in mice. It showed potential antipsychotic activity, but no antidepressant or anxiolytic actions.

E-52862, also known as sigma-1 receptor antagonist (API-001, S1RA) successfully completed Phase I clinical trials for the treatment of pain, showing good safety and tolerability, and a pharmacokinetic profile compatible with once a day oral administration.

Acetophenazine (Tindal) is an antipsychotic drug of moderate-potency. Used in the treatment of disorganized and psychotic thinking. Acetophenazine (Tindal) is also used to help treat false perceptions (e.g. hallucinations or delusions). Acetophenazine acts as an antagonist of dopaminergic D2 receptors in the brain. Acetophenazine exhibited modest androgen receptor binding and antiandrogen activity.