In Vitro and In Vivo Characterization of the Alkaloid Nuciferine. PLoS One 2016;11(3):e0150602
Date
03/11/2016Pubmed ID
26963248Pubmed Central ID
PMC4786259DOI
10.1371/journal.pone.0150602Scopus ID
2-s2.0-84962584770 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
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.
Author List
Farrell MS, McCorvy JD, Huang XP, 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 BLAuthor
John McCorvy PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntipsychotic Agents
Aporphines
Behavior, Animal
HEK293 Cells
Humans
Mice
Receptors, Dopamine D4
Serotonin 5-HT1 Receptor Agonists
