title: In Vitro and In Vivo Characterization of the Alkaloid Nuciferine.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Martilias S
authors.initials: MS
authors.lastname: Farrell
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: McCorvy
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.|National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Xi-Ping
authors.initials: XP
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Urban
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Kate L
authors.initials: KL
authors.lastname: White
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Giguere
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Allison K
authors.initials: AK
authors.lastname: Doak
authors.affiliation: Department of Environmental Health, Rollins School of Public Health and Center for Neurodegenerative Diseases, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Alison I
authors.initials: AI
authors.lastname: Bernstein
authors.affiliation: Department of Environmental Health, Rollins School of Public Health and Center for Neurodegenerative Diseases, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Stout
authors.affiliation: Departments of Psychiatry and Behavioral Sciences, Cell Biology, and Neurobiology, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Su Mi
authors.initials: SM
authors.lastname: Park
authors.affiliation: Departments of Psychiatry and Behavioral Sciences, Cell Biology, and Neurobiology, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Ramona M
authors.initials: RM
authors.lastname: Rodriguiz
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Bradley W
authors.initials: BW
authors.lastname: Gray
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: William S
authors.initials: WS
authors.lastname: Hyatt
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Norwood
authors.affiliation: Department of Psychology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Webster
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Gannon
authors.affiliation: Department of Environmental Health, Rollins School of Public Health and Center for Neurodegenerative Diseases, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Miller
authors.affiliation: Department of Psychology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Porter
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Shoichet
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Fantegrossi
authors.affiliation: Departments of Psychiatry and Behavioral Sciences, Cell Biology, and Neurobiology, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: William C
authors.initials: WC
authors.lastname: Wetsel
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.|Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.|Program in Neuroscience, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.|Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.|Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.|Division of Chemical Biology and Medicinal Chemistry, School of Pharmacy, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.|National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001060:Aporphines / Q000737:chemistry* / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D050638:Receptors, Dopamine D4 / Q000819:agonists; D058825:Serotonin 5-HT1 Receptor Agonists / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D001060:Aporphines; D058825:Serotonin 5-HT1 Receptor Agonists; D050638:Receptors, Dopamine D4; C008692:nuciferine