Aplindore (DAB-452) is a small molecule that displays potent dopamine D2 receptor partial agonist activity in in vitro and in vivo assays and is predicted to have antipsychotic efficacy without motor side effects. Aplindore had been in phase II clinical trials for the treatment of Parkinson's disease and restless legs syndrome. Aplindore was generally well tolerated and there were no withdrawals due to adverse events and no serious adverse events.

Fananserin is a potential antipsychotic compound with a high affinity for both D4 and 5-HT2A receptors, and negligible affinity for D2 receptors. Fananserin has been researched for the treatment of schizophrenia. Fananserin was the first selective D4/5-HT2A antagonist to undergo clinical trials for schizophrenia. It has a high affinity for D4 (Ki 2.9 nM) and 5-HT2A (Ki 0.37 nM) receptors and is over 100-fold selective versus H1, a1 adrenergic, 5-HT1A and D2 dopamine receptors. Development of this compound was halted following phase II clinical trials due to lack of efficacy.

Sonepiprazole exhibits highly specific binding to the D4 dopamine receptor with more than 100-fold selectivity for the D4 receptor over other receptors, including dopamine, serotonin, and adrenergic receptors. It is a neutral antagonist at the D4 dopamine receptor and is devoid of dopamine agonist activity. Sonepiprazole selectively induces c-fos expression in the prefrontal cortex and blocks behavioral, biochemical, and genomic effects of repeated amphetamine administration in rats. Sonepiprazole was investigated as an antipsychotic for the treatment of schizophrenia in a placebo-controlled clinical trial, but in contrast to its comparator olanzapine no benefits were found and it was not researched further for this indication.

CP 226269 is a selective dopamine D4 agonist. This compound was developed by Pfizer for Neuroscience research. CP226269 showed a significant enhancement in the 5-trial inhibitory avoidance model.