Dopamine receptor signaling and current and future antipsychotic drugs

Kevin N. Boyd, Richard B. Mailman

Research output: Chapter in Book/Report/Conference proceedingChapter

40 Scopus citations

Abstract

All currently efficacious antipsychotic drugs have as part of their mechanism the ability to attenuate some or all of the signaling through the dopamine D2 receptor. More recently, the dopamine D1 receptor has been hypothesized to be a promising target for the treatment of negative and/or cognitive aspects of schizophrenia that are not improved by current antipsychotics. Although cAMP has been presumed to be the primary messenger for signaling through the dopamine receptors, the last decade has unveiled a complexity that has provided exciting avenues for the future discovery of antipsychotic drugs (APDs). We review the signaling mechanisms of currently approved APDs at dopamine D2 receptors, and note that aripiprazole is a compound that is clearly differentiated from other approved drugs. Although aripiprazole has been postulated to cause dopamine stabilization due to its partial D2 agonist properties, a body of literature suggests that an alternative mechanism, functional selectivity, is of primary importance. Finally, we review the signaling at dopamine D1 receptors, and the idea that drugs that activate D1 receptors may have use as APDs for improving negative and cognitive symptoms. We address the current state of drug discovery in the D1 area and its relationship to novel signaling mechanisms. Our conclusion is that although the first APD targeting dopamine receptors was discovered more than a half-century ago, recent research advances offer the possibility that novel and/or improved drugs will emerge in the next decade.

Original languageEnglish (US)
Title of host publicationCurrent Antipsychotics
EditorsGerhard Gross, Gerhard Gross, Mark A. Geyer
Pages53-86
Number of pages34
DOIs
StatePublished - Dec 3 2012

Publication series

NameHandbook of Experimental Pharmacology
Volume212
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Boyd, K. N., & Mailman, R. B. (2012). Dopamine receptor signaling and current and future antipsychotic drugs. In G. Gross, G. Gross, & M. A. Geyer (Eds.), Current Antipsychotics (pp. 53-86). (Handbook of Experimental Pharmacology; Vol. 212). https://doi.org/10.1007/978-3-642-25761-2-3