Dopamine D-2 activity of R-(-)-apomorphine and selected analogs: a microdialysis study

In the present study, R-(-)-apomorphine and three of its analogs were studi ed for their potency in decreasing the release of dopamine in the striatum after subcutaneous administration and for their oral bioavailability using the microdialysis technique in freely moving rats. The analogs R-(-)-N-n-propylnorapomorphine and R-(-)-11-hydroxy-N-n-propyln oraporphine displayed a higher potency than R-(-)-apomorphine in decreasing the release of dopamine in the striatum. A high dose of R-(-)-11-hydroxyap orphine, a dopamine D-2 receptor partial agonist, had a small effect on the release of dopamine in the striatum. The catechols R-(-)-N-n-propylnorapom orphine and R-(-)-apomorphine displayed a comparable oral bioavailability ( 1%), while the mono-hydroxy analog R-(-)-11-hydroxy-N-n-propylnoraporphine displayed a slightly higher oral bioavailability (3%). In conclusion, R-(-)-N-n-propylnorapomorphine and R-(-)-11-hydroxy-N-n-prop ylnoraporphine did not show a substantial improvement in bioavailability. H owever, due to the clear difference in their efficacy in decreasing dopamin e release, in spite of the similar agonist binding affinities to the dopami ne D-2 receptor of the two analogs compared to R-(-)-apomorphine, they coul d be useful alternatives for apomorphine in the treatment of Parkinson's di sease. (C) 2000 Elsevier Science B.V. All rights reserved.