In Vitro and In Vivo Characterization of the Alkaloid Nuciferine.

Journal Article (Journal Article)

RATIONALE: The sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays. METHODS: Nuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms. RESULTS: Nuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A 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. CONCLUSIONS: The molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions.

Full Text

Duke Authors

Cited Authors

  • Farrell, MS; McCorvy, JD; Huang, X-P; Urban, DJ; White, KL; Giguere, PM; Doak, AK; Bernstein, AI; Stout, KA; Park, SM; Rodriguiz, RM; Gray, BW; Hyatt, WS; Norwood, AP; Webster, KA; Gannon, BM; Miller, GW; Porter, JH; Shoichet, BK; Fantegrossi, WE; Wetsel, WC; Roth, BL

Published Date

  • 2016

Published In

Volume / Issue

  • 11 / 3

Start / End Page

  • e0150602 -

PubMed ID

  • 26963248

Pubmed Central ID

  • PMC4786259

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0150602


  • eng

Conference Location

  • United States