In Vitro and In Vivo Characterization of the Alkaloid Nuciferine

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  • Farrell, Martilias S.
    • Affiliation: School of Medicine, Department of Pharmacology
  • McCorvy, John D.
    • Affiliation: School of Medicine, Department of Pharmacology
  • Huang, Xi-Ping
    • Affiliation: School of Medicine, Department of Pharmacology
    • Other Affiliation: NIMH Psychoactive Drug Screening Program
  • Urban, Daniel J.
    • Affiliation: School of Medicine, Department of Pharmacology
  • White, Kate L.
    • Affiliation: School of Medicine, Department of Pharmacology
  • Giguere, Patrick M.
    • Affiliation: School of Medicine, Department of Pharmacology
  • Doak, Allison K.
    • Other Affiliation: Department of Pharmaceutical Chemistry; University of California San Francisco
  • Bernstein, Alison I.
    • Other Affiliation: Department of Environmental Health; Rollins School of Public Health; Center for Neurodegenerative Diseases; Emory University
  • Stout, Kristen A.
    • Other Affiliation: Department of Environmental Health; Rollins School of Public Health; Center for Neurodegenerative Diseases; Emory University
  • Park, Su Mi
    • Other Affiliation: Department of Psychiatry and Behavioral Sciences; Cell Biology; and Neurobiology; Mouse Behavioral and Neuroendocrine Analysis Core Facility; Duke University Medical Center
  • Rodriguiz, Ramona M.
    • Other Affiliation: Department of Psychiatry and Behavioral Sciences; Cell Biology; and Neurobiology; Mouse Behavioral and Neuroendocrine Analysis Core Facility; Duke University Medical Center
  • Gray, Bradley W.
    • Other Affiliation: Department of Pharmacology and Toxicology; University of Arkansas for Medical Sciences
  • Hyatt, William S.
    • Other Affiliation: Department of Pharmacology and Toxicology; University of Arkansas for Medical Sciences
  • Norwood, Andrew P.
    • Other Affiliation: Department of Pharmacology and Toxicology; University of Arkansas for Medical Sciences
  • Webster, Kevin A.
    • Other Affiliation: Department of Psychology; Virginia Commonwealth University
  • Gannon, Brenda M.
    • Other Affiliation: Department of Pharmacology and Toxicology; University of Arkansas for Medical Sciences
  • Miller, Gary W.
    • Other Affiliation: Department of Environmental Health; Rollins School of Public Health; Center for Neurodegenerative Diseases; Emory University
  • Porter, Joseph H.
    • Other Affiliation: Department of Psychology; Virginia Commonwealth University
  • Shoichet, Brian K.
    • Other Affiliation: Department of Pharmaceutical Chemistry; University of California San Francisco
  • Fantegrossi, William E.
    • Other Affiliation: Department of Pharmacology and Toxicology; University of Arkansas for Medical Sciences
  • Wetsel, William C.
    • Other Affiliation: Department of Psychiatry and Behavioral Sciences; Cell Biology; and Neurobiology; Mouse Behavioral and Neuroendocrine Analysis Core Facility; Duke University Medical Center
  • Roth, Bryan L.
    • Affiliation: School of Medicine, Department of Pharmacology
    • Other Affiliation: Department of Psychiatry
Abstract
  • RationaleThe 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.MethodsNuciferine 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.ResultsNuciferine 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.ConclusionsThe 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.
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  • Article
Rights statement
  • In Copyright
Journal title
  • PloS One
Journal volume
  • 11
Journal issue
  • 3
Page start
  • e0150602
Language
  • English
ISSN
  • 1932-6203

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