The tetrahydroisoquinoline derivative SB269,652 is an allosteric antagonist at dopamine D3 and D2 receptors.

ABSTRACT: In view of the therapeutic importance of dopamine D(3) and D(2) receptors, there remains considerable interest in novel ligands. Herein, we show that the tetrahydroisoquinoline 1H-indole-2-carboxylic acid {4-[2-(cyano-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-cyclohexyl}-amide (SB269,652) behaves as an atypical, allosteric antagonist at D(3) and D(2) receptors. Accordingly, SB269,652 potently (low nanomolar range) abolished specific binding of [(3)H]nemanopride and [(3)H]spiperone to Chinese hamster ovary-transfected D(3) receptors when radioligands were used at 0.2 and 0.5 nM, respectively. However, even at high concentrations (5 μM), SB269,652 only submaximally inhibited the specific binding of these radioligands when they were employed at 10-fold higher concentrations. By analogy, althoug

SUBMITTER: Silvano E 

PROVIDER: S-EPMC2981362 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature