(Aryloxy)alkylamines as selective human dopamine D4 receptor antagonists: potential antipsychotic agents.
Article Details
- CitationCopy to clipboard
Unangst PC, Capiris T, Connor DT, Doubleday R, Heffner TG, MacKenzie RG, Miller SR, Pugsley TA, Wise LD
(Aryloxy)alkylamines as selective human dopamine D4 receptor antagonists: potential antipsychotic agents.
J Med Chem. 1997 Dec 5;40(25):4026-9.
- PubMed ID
- 9406594 [ View in PubMed]
- Abstract
The discovery of a series of novel (aryloxy)alkylamines with selective affinity for the dopamine D4 receptor is described. Target compounds were tested for binding to cloned human dopamine D2, D3, and D4 receptor subtypes expressed in Chinese hamster ovary (CHO) K-1 cells. A number of compounds demonstrated subnanomolar Ki values for binding to the D4 receptor, with several 100-fold selectivities toward the D2 and D3 receptors. Several compounds with combined D3/D4 receptor binding selectivity were also identified. A limited structure-activity relationship study of this chemical series is discussed. In a mitogenesis functional assay, the effect of the test compounds on cellular uptake of [3H]thymidine in D4-transfected CHO 10,001 cells was measured and compared to the response of the full dopamine agonist quinpirole. The activity of the compounds varied from full antagonist to weak partial agonist activity (intrinsic activity of 0-19% in comparison to quinpirole).
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Clozapine Dopamine D2 receptor Ki (nM) 91 N/A N/A Details Clozapine Dopamine D3 receptor Ki (nM) 222 N/A N/A Details Clozapine Dopamine D4 receptor Ki (nM) 16 N/A N/A Details Haloperidol Dopamine D2 receptor Ki (nM) 1.6 N/A N/A Details Haloperidol Dopamine D3 receptor Ki (nM) 2.2 N/A N/A Details