THE PREFERENTIAL DOPAMINE D-3 RECEPTOR-LIGAND, (+)-UH 232, IS A PARTIAL AGONIST

In a NG 108 15 hybrid cell line stably expressing a recombinant dopamine D-3 receptor, (+)-UH 232 (cis-(+)-1S,2R)-5-methoxy-1-methyl-2-(di-n-propylamino)tet a partially selective D-3 receptor ligand, stimulates mitogenesis, as measured by incorporation of [H-3]thymidine, with an EC(50) of 7.6 nM and a maximal increase corresponding to 23% of the response elicited by quinpirole, a full agonist. This effect was antagonised by nafadotride, a D-3 receptor-selective antagonist. (+)-UH 232 also antagonised quinpirole-induced mitogenesis with a Xi value of 9.4 nM. (+)-UH 232(1 mu M) inhibited by 22% the forskolin-induced accumulation of cAMP, whilst the inhibition by quinpirole (100 nM) was 53%. These results indicate that (+)-UH 232 is a partial agonist at the D-3 receptor with an intrinsic activity of 0.2-0.4.