Emetic activity of N-substituted norapomorphines

Norapomorphine and ten of its N-substituted derivatives were prepared by modifications of procedures described earlier. In a dog emesis test the N-ethyl and N-n-propyl compounds had minimum effective doses of 0.00025 and 0.0005 mg/kg, respectively, when administered iv, sc, or im. In a modified Irwin mouse profile screen the minimum effective iv dose was 0.013 mg/kg for the N-ethyl and 0.0024 mg/kg for the N-n-propyl compound; percutaneous absorption was also observed in mice. All compounds examined caused the stereotyped apomorphine behavior syndrome but hypotensive effects were not serious.