Nuciferine

Nuciferine is an antagonist at 5-HT_2A (IC₅₀=478 nM), 5-HT_2C (IC₅₀=131 nM), and 5-HT_2B (IC₅₀=1 μM), an inverse agonist at 5-HT₇ (IC₅₀=150 nM), a partial agonist at D₂ (EC₅₀=64 nM), D₅ (EC₅₀=2.6 μM) and 5-HT₆ (EC₅₀=700 nM), an agonist at 5-HT_1A (EC₅₀=3.2 μM) and D₄ (EC₅₀=2 μM) receptor. IC50 & Target:IC50: 131 nM (5-HT_2C receptor), 150 nM (5-HT₇ receptor), 478 nM (5-HT_2A receptor), 1 μM (5-HT_2B receptor)^[1]
EC50: 64 nM (D₂ receptor), 2.6 μM (D₅ receptor), 700 nM (5-HT₆ receptor),3.2 μM (5-HT_1A receptor), 2 μM (D₄ receptor)^[1] In Vitro: Nuciferine is a partial agonist at DD₂ 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^[1]. 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^[2]. In Vivo: 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 ED₅₀ 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)^[1].