Treatment of Parkinson's Disease with Aporphines

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Abstract
To avoid the main drawbacks of prolonged treatment with levodopa (involuntary movements and the "on-off" phenomenon), we administered apomorphine by mouth to 14 patients with Parkinson's disease. This treatment caused azotemia, which we circumvented by switching to N-propylnoraporphine, whose nephrotoxic dose (80 mg six times per day) was larger than its therapeutic dose (10 to 15 mg six times per day). Slowly increasing doses induced significant improvement (P < 0.005) in all 24 patients studied, transitory mental aberrations in seven, and release of growth hormone in three patients tested. In patients previously on prolonged levodopa administration, the dyskinesia and "on-off" phenomenon were almost identical with N-propylnoraporphine, but both drawbacks were reduced or abolished in six patients by coadministration of α-methyldopa hydrazine plus levodopa. This coadministration seemed to abolish tachyphylaxis. We conclude that N-propylnoraporphine is very useful In the treatment of Parkinson's disease. (N Engl J Med 294:567–572, 1976)