Aporphines. 34. (-)-2,10,11-Trihydroxy-N-n-propylnoraporphine, a novel dopaminergic aporphine alkaloid with anticonvulsant activity

Article abstract of DOI:10.1021/jm00139a027

(-)-2,10,11-Trihydroxy-N-n-propylnoraporphine (TNPA, 2c) has been synthesized from thebaine (3a), via northebaine (3b), normophothebaine (2a), and alkylation to the N-propyl derivative 2b. O-Demethylation gave the desired product 2c. Compound 2c showed activity comparable to its 10,11-dihydroxy counterpart (NPA, 1b) on the stimulation of dopamine-sensitive adenylate cyclase in carp retinal homogenates. The evaluation of 2c on audiogenic seizures in mice, in the protection against paroxysimal EEG and myoclonic response to photic stimulation in the baboon, revealed a similar pharmacological profile in comparison to NPA and apomorphine, with TNPA showing a prolonged duration of action in abolishing myoclonic response to photic stimulation in the baboon.