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

Abstract

(-)-2,10,11-Trihydroxy-N-n-propylnoraporphine (TNPA, 2c) was synthesized from thebaine, via northebaine, normorphothebaine and alkylation to the N-propyl derivative. 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 responses to photic stimulation in the baboon.