Dopamine receptors are a class of G protein-coupled receptors (GPCR) that are prominent in the vertebrate central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors. Dopamine receptors are implicated in many neurological processes, including motivation, pleasure, cognition, memory, learning, and fine motor control, as well as modulation of neuroendocrine signaling. Abnormal dopamine receptor signaling and dopaminergic nerve function is implicated in several neuropsychiatric disorders. Dopamine receptors are common neurologic drug targets; antipsychotics are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors.

D2-like class dopamine receptors are coupled to Gαi/o and thus inhibits adenylate cyclase production. Unlike the D1-like class, D2-like receptors are found pre and post-synaptically. Receptor dysfunction is recognized as a core alteration in several neurological and psychiatric disorders, including Parkinson's disease (PD) and associated movement disorders, as well as, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD) and addiction (Seeman 2010, Boyd & Mailman 2012). All current antipsychotic drugs (APDs) have some degree of D2 antagonism as part of their pharmacological profile. A dopamine antagonist (antidopaminergic) is a type of drug which blocks dopamine receptors by receptor antagonism (Kapur et al. 2000, Seeman 2002). Carlsson & Lindqvist (1963) showed that chlorpromazine binds to postsynaptic dopamine receptors, and supported the hypothesis that symptoms of schizophrenia could be treated by blocking dopamine receptors in post-synaptic neurons. This revolutionized the treatment of psychiatric disorders. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting (Boyd & Mailman 2012). Nearly 30% of patients with schizophrenia do not respond to antipsychotic treatment and the underlying neurobiological causes are unknown (Amato et al. 2019).

D2-APDs can be very broadly characterized as "typical/first generation" or "atypical/second generation" (Leucht et al. 2009). Typical antipsychotics were first developed in the 1950s and used to treat psychosis, in particular, schizophrenia) and also for the treatment of acute mania and agitation. Atypical antipsychotics were introduced after the 1970s and are used to treat schizophrenia or bipolar disorder. Atypicals are less likely than typicals to cause extrapyramidal motor control disabilities but they can still have severe side effects. It is debatable whether, as a class, typical or atypical antipsychotics are better so an individualised treatment approach is required (Bonham & Abbott 2008).

Typical D2-APDs include chlorpromazine, mesoridazine, promazine, Loxapine, perphenazine, flupentixol, fluphenazine, haloperidol, pimozide, prochlorperazine, trifluoperazine, benperidol, fluspirilene and thioridazine. Atypical D2-APDs include amisulpride, asenapine, aripiprazole, clozapine, blonanserin, cariprazine, iloperidone, olanzapine, quetiapine, risperidone, sertindole, sulpiride, ziprasidone, perospirone, pipotiazine, zotepine, terguride,
amisulpride and domperidone.