The distribution of the D2 family of dopamine receptors in human brain argues for an interest in the D3 and D4 receptors in schizophrenia. The D4 receptor is not only the prime target for clozapine but also highly and differentially localized to the neocortex, thalamus, and hippocampus. These are central nervous system areas of direct interest in schizophrenia. The initial therapeutic directions in this area will target receptor antagonists. Moreover, because the D3 receptor may mediate functional actions opposite those mediated by the D2 receptor, its pharmacology in schizophrenia may also be important. The use of selective antagonists to test these concepts is important. Partial agonists at these different receptors should eventually be targeted and tested in schizophrenia since these drugs could have antagonist (antipsychotic) effects without any antagonist side effects. We report early results of tests with (-)-3PPP, which suggest that there is some antipsychotic action, even though tolerance and uneven clinical actions are apparent. These areas are only beginning to be explored in schizophrenia and require much more research to fully exploit. Drugs that are available to the clinician that act selectively at the D2-, D3-, and D4-receptor sites will be essential in this work.
- Agonists and partial agonists
- D- and D-receptor antagonists
ASJC Scopus subject areas
- Clinical Neurology
- Pharmacology (medical)