DOPAMINE AGONISTS USED IN THE TREATMENT OF PARKINSONS-DISEASE AND THEIR SELECTIVITY FOR THE D-1 D-2, AND D-3 DOPAMINE-RECEPTORS IN HUMAN STRIATUM

1. It has been suggested that an ideal antiparkinsonian treatment requires stimulation of both D-1 and D-2 dopamine receptors. Bromocriptine and lisuride are regarded as pure D-2 receptor agonists, whereas pergolide and apomorphine are thought to stimulate both D-1 and D-2 receptors. 2. The aim of this study was to compare the affinities of bromocriptine, lisuride, pergolide, and apomorphine for the D-1, D-2, and D-3 receptors in postmortem human striatum. The dissociation constants (K-i values) of the dopamine agonists were determined from competition binding experiments with selective radioligands. 3. The K-i values of the orally administered agonists - bromocriptine, pergolide, and lisuride - for the D-2 receptors were proportional to their optimal doses against parkinsonism. K-i(D-1)/K-i(D-2) ratios were 23 for lisuride, 67 for pergolide, 60 for bromocriptine, and 2.6 for apomorphine. K-i(D-3)/K-i(D-2) ratios were 0.4 for lisuride, 1 for pergolide, 5.4 for bromocriptine, and 21 for apomorphine. 4. The present results support the hypothesis that the antiparkinsonian effect of dopamine agonists is mediated primarily by D-2 receptors. Apomorphine is a mixed D-1/D-2 agonist, but pergolide has no more D-1 agonist properties than bromocriptine and lisuride. The role of the D-3 receptors is unknown, but their activation might either be associated with the generation of psychiatric side-effects or dyskinesias, or alternatively add to antiparkinsonian activity.