SDZ-PSD-958, A NOVEL D-1 RECEPTOR ANTAGONIST WITH POTENTIAL LIMBIC SELECTIVITY

SDZ PSD 958, a never benzo[g]quinoxaline derivative exhibits the prope rties of a potent orally active selective D-1 receptor antagonist. It has high affinity for D-1-like receptors (D-1, D-5; pKi = 9.7-9.8) lab elled by [H-3]SCH23390 and is at least 400 fold less active at D-2-lik e receptors (i.e. D-2, D-4) labelled by [H-3]spiperone. Effects in fun ctional tests are consistent with D-1 receptor antagonist properties. SDZ PSD 958 inhibited apomorphine-induced rearing in mice and prevente d prolongation of novelty-induced locomotion in rats elicited by the s elective D-1 receptor agonist CY 208-243. By contrast, SDZ PSD 958 did not induce catalepsy and only weakly inhibited apomorphine-induced st ereotyped gnawing in rats. This suggests that SDZ PSD 958 preferential ly inhibits responses mediated by dopamine systems innervating the lim bic system.