荷叶碱

Nuciferine is a partial agonist at DD ₂ receptor with an activity (E _max =67% of dopamine) similar to aripiprazole (E _max =50% of dopamine). In line with its partial agonist activity, Nuciferine inhibited dopamine-induced activation of G _i with a potency similar to clozapine (Nuciferine K _B =62 nM; Clozapine K _B =20 nM) as determined via Schild regression analysis. The natural product Nuciferine acts as an effective inhibitor of adult worm motility. Nuciferine is effective at inhibiting both basal and 5-HT evoked motility of adult schistosomes. Nuciferine inhibits Sm.5HTR _L and schistosomule with 0.24±0.04 and 0.62±0.22 μM, respectively.

In rodent models relevant to antipsychotic drug action, Nuciferine blocks head-twitch responses and discriminative stimulus effects of a 5-HT _2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy. In the presence of 1 or 3 mg/kg Nuciferine, cumulative PCP doses produce similar substitution to PCP alone. In the clozapine-trained animals, a dose-dependent substitution for 1.25 mg/kg clozapine is seen at 10 mg/kg Nuciferine (80.63% drug lever responding), with an ED ₅₀ value of 5.42 mg/kg (95% CI 3.09-9.48 mg/kg) while the lower doses tested (0.1 mg/kg-3 mg/kg) fails to produce substitution for clozapine’s discriminative cue. In addition to a high percentage of responding on the clozapine-appropriate lever, 10 mg/kg Nuciferine also produces significant rate suppression as compared to vehicle control points (p<0.001).