Dopamine D3 receptor ligands with antagonist properties.

Abstract	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.
Authors	Anneke E Hackling, Holger Stark
Journal	Chembiochem : a European journal of chemical biology (Chembiochem) Vol. 3 Issue 10 Pg. 946-61 (Oct 04 2002) ISSN: 1439-4227 [Print] Germany
PMID	12362359 (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
Topics	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)

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