The preferential dopamine D 3 receptor ligand, (+)-UH232, is a partial agonist

Abstract

In a NG 108 15 hybrid cell line stably expressing a recombinant dopamine D 3 receptor, (+)-UH 232 ( cis-(+)-1 S,2 R)-5-methoxy-1-methyl-2-(di- n-propylamino)tetralin), a partially selective D 3 receptor ligand, stimulates mitogenesis, as measured by incorporation of [ 3H]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 K i value of 9.4 nM. (+)-UH 232 (1 μM) 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.