Dopamine D3 receptor ligands with antagonist properties.

The dopamine D(3) receptor has been recognized to play an important role in the molecular mechanisms of various neuropsychiatric disorders. The development of new dopamine D(3) receptor selective antagonists is premised on the potentially improved therapeutic treatment of psychosis like schizophrenia. Partial agonists at dopamine D(3) receptors are supposed to be beneficial when administered to drug abusers or in Parkinson's disease. The structural basis for most compounds is at least a basic, aryl-substituted alkanamine part with an alkyl moiety, which in many compounds forms a spacer to another aryl residue. Structural variety among the amine moiety includes aminotetralins, tetrahydroisoquinolines, isoindoles, benzazepines, and aminoindans, as well as pyrrolidines, pyrroles, and 4-phenylpiperazines. Various ways for lead optimization are shown in different classes of compounds. Promising ligands with high D(3) receptor affinity often lack sufficient selectivity or display deficits in the required in vivo parameters. Structure-activity relationships for dopamine D(3) receptor antagonists and partial agonists are discussed here, along with the outlook for their potential therapeutic application.
AuthorsAnneke E Hackling, Holger Stark
JournalChembiochem : a European journal of chemical biology (Chembiochem) Vol. 3 Issue 10 Pg. 946-61 (Oct 4 2002) ISSN: 1439-4227 [Print] Germany
PMID12362359 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)
Chemical References
  • Amides
  • Benzazepines
  • Dopamine D2 Receptor Antagonists
  • Drd3 protein, rat
  • Indans
  • Isoquinolines
  • Ligands
  • Piperazines
  • Pyrroles
  • Pyrrolidines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Tetrahydronaphthalenes
  • pyrrolidine
  • Amides (chemistry, pharmacology)
  • Animals
  • Benzazepines (chemistry, pharmacology)
  • Dopamine D2 Receptor Antagonists
  • Drug Design
  • Indans (chemistry, pharmacology)
  • Isoquinolines (chemistry, pharmacology)
  • Ligands
  • Piperazines (chemistry, pharmacology)
  • Pyrroles (chemistry, pharmacology)
  • Pyrrolidines (chemistry, pharmacology)
  • Rats
  • Receptors, Dopamine D2 (agonists, chemistry, metabolism)
  • Receptors, Dopamine D3
  • Structure-Activity Relationship
  • Substrate Specificity
  • Tetrahydronaphthalenes (chemistry, pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: