LOWER EFFICACY OF THE DOPAMINE-D1 AGONIST, SKF-38393, TO STIMULATE ADENYLYL CYCLASE ACTIVITY IN PRIMATE THAN IN RODENT STRIATUM

The selective D1 agonist, SKF 38393, stimulated adenylyl cyclase by about 40% of basal activity in rat striatum but by only about 10% in the striatum of rhesus monkeys. In contrast, dopamine stimulated striatal adenylvl cyclase in both species with equal efficiency (70-80%). SKF 38393 30-mu-M inhibited the effect of 30-mu-M dopamine by about 45% in rat and by about 75% in primate tissue. This difference may be due to a lower D1 receptor reserve in primate than in rodent tissue and suggests that only selective D1 agonists with full efficacy at D1 receptors can be expected to have beneficial effects in patients with Parkinson's disease.