Identification of agents displaying functional activation of dopamine d2 and d4 receptors

Abstract

A method of treating psychosis, and the underlying antipsychotic formulation. The method includes administering a therapeutically effective amount of synthetic agents that selectively recruit β-arrestin to D2 receptors and have little-to-no binding to culprit receptors associated with weight gain and Type II diabetes. The synthetic agents can include SYA16263 and SYA16264, and/or derivatives or analogs thereof. The 1-(pyridin-2-yl)piperazine moiety was found to play a significant role in recruiting β-arrestin to D2 receptors. In other embodiments, the current invention relates to synthetic agents that are selective of D4 receptors for treatment of psychosis and erectile dysfunction. The synthetic agents can include SYA27287 and/or derivatives or analogs thereof. In all embodiments, extrapyramidal side effects are eliminated or minimized.

What is claimed is: 
     
         1 . A method of treating erectile dysfunction in a subject in need thereof comprising:
 administering to the subject, a therapeutically effective amount of a selective dopamine D4 receptor agonist compound.   
     
     
         2 . The method of  claim 1 , wherein the selective dopamine D4 receptor agonist compound is 2-(3-(4-(Pyrimidin-2-yl)piperazin-1-yl)propyl)benzo[d]thiazole trihydrobromide or an analogue thereof. 
     
     
         3 . The method of  claim 1 , wherein the selective dopamine D4 receptor agonist compound has little to no affinity for D1, D2, D3, or D5 dopamine receptors. 
     
     
         4 . The method of  claim 1 , wherein the therapeutically effective amount is at least about 1 mg/kg. 
     
     
         5 . A method of  claim 1 , wherein the selective dopamine D4 receptor agonist compound is administered as part of a composition including a pharmaceutically acceptable carrier. 
     
     
         6 . The method of  claim 5 , wherein the composition is administered parenterally or subcutaneously to the subject.