SDZ-GLC-756, A NOVEL OCTAHYDROBENZO[G]QUINOLINE DERIVATIVE EXERTS OPPOSING EFFECTS ON DOPAMINE D-1 AND D-2 RECEPTORS

SDZ GLC-756, a novel octahydrobenzo[g]quinoline derivative, is equipot ent in displacing [H-3]SCH23390 from dopamine D-1 receptors and [H-3]2 05-501 from dopamine D-2 receptor binding sites. It blocks dopamine se nsitive adenylate cyclase with the same potency as SCH23390, indicatin g antagonist properties at dopamine D-1 receptors. On the other hand, SDZ GLC 756 inhibits electrically evoked acetylcholine release from ra t striatal slices with the same potency as the selective dopamine D-2 receptor agonist bromocriptine. This effect is blocked by spiperone su ggesting that it is mediated by dopamine D-2 receptor activation. The opposing action of SDZ GLC 756 on dopamine D-1 and D-2 receptors is al so evident in vivo. SDZ GLC 756, like SCH23390, blocks apomorphine-ind uced rearing in mice. On the other hand, it inhibits prolactin secreti on and produces circling in unilateral 6-OHDA-lesioned rats, which is compatible with stimulant properties at dopamine D-2 receptors. This d rug might be a new tool to study linkage between dopamine D-1 and D-2 receptors.