One major issue is that the increased release of dopamine in schizophrenia is supposed to hit both classes of dopamine receptors, D1- and D2-like, and on the other side, all antipsychotics, with few exceptions (asenapine and clozapine), have relatively low affinity for D1R compared to D2R affinity and occupancy/antagonism. Here, DRD1 is linked to schizophrenia.