DOPAMINE-RECEPTOR SUBTYPE-SELECTIVE AGONISTS IN THE TREATMENT OF PARKINSONS-DISEASE

Dopamine agonists have a number of potential advantages over levodopa in the symptomatic treatment of Parkinson's disease. To evaluate wheth er the relative affinity of an agonist for the D-1, D-2, and D-3 subty pes of dopamine receptors influences its antiparkinsonian or dyskinesi ogenic effect, results with levodopa were compared with those of three dopamine agonists having differing binding profiles. The antiparkinso nian response to apomorphine tended to be slightly but not significant ly lower than with levodopa, whereas the response to both N-propyl-nor apomorphine (NPA) and N-0923 averaged approximately 33% lower than tha t for levodopa. The severity of choreiform dyskinesias induced by the latter two agonists also tended to be somewhat less than those associa ted with levodopa. The ratio of dyskinesias to antiparkinsonian effica cy for levodopa and all the agonists evaluated were thus very similar. Evaluation of the clinical results for these dopaminomimetics with re spect to their dopamine receptor affinity profile suggests that compar able binding affinities for the D-1 and D-2 receptors may be associate d with greater antiparkinsonian activity, which tends to diminish as r elative D-2 selectivity is enhanced. A relatively high affinity for D- 2 or D-3 receptors appears to be associated with a diminished antipark insonian response, which in both cases is associated with a somewhat r educed tendency to induce dyskinesias. A relative affinity for the D-1 receptor appears to have little effect on either antiparkinsonian act ivity or the potential for dyskinesias. It is conceivable that D-1/D-2 /D-3-nonselective agonists that approximate the receptor affinity prof ile of dopamine might prove most advantageous in patients with parkins onism.