Nuciferine

Names

IUPAC name 1,2-Dimethoxy-6aβ-aporphine
Systematic IUPAC name (6aR)-1,2-Dimethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzoquinoline
Other names (R)-1,2-Dimethoxyaporphine
Identifiers
CAS Number	475-83-2 Y
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL464529 N
ChemSpider	9740 N
PubChem CID	10146
UNII	W26UEB90B7 Y
CompTox Dashboard (EPA)	DTXSID40963862
InChI InChI=1S/C19H21NO2/c1-20-9-8-13-11-16(21-2)19(22-3)18-14-7-5-4-6-12(14)10-15(20)17(13)18/h4-7,11,15H,8-10H2,1-3H3/t15-/m1/s1 NKey: ORJVQPIHKOARKV-OAHLLOKOSA-N N InChI=1/C19H21NO2/c1-20-9-8-13-11-16(21-2)19(22-3)18-14-7-5-4-6-12(14)10-15(20)17(13)18/h4-7,11,15H,8-10H2,1-3H3/t15-/m1/s1Key: ORJVQPIHKOARKV-OAHLLOKOBA
SMILES CN(CC1)2()CC3=CC=CC=C3C4=C2C1=CC(OC)=C4OC
Properties
Chemical formula	C19H21NO2
Molar mass	295.376 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). N verify (what is YN ?) Infobox references

Nuciferine is an alkaloid found within the plants Nymphaea caerulea and Nelumbo nucifera.

Preliminary psychopharmacological research in 1978 was unable to conclusively determine the compound's classification regarding dopamine-receptor activity. On one hand, investigative studies found evidence of behavior traditionally associated with dopamine-receptor stimulation: stereotypy, increase in spontaneous motor activity, inhibition of conditioned avoidance response, and an increase in pain sensitivity resulting in an inhibition of morphine analgesia. On the other hand, these early investigative studies also found evidence of behavior traditionally associated with dopamine-receptor blockade: decrease of spontaneous motor activity, chills, catalepsy, trance-like states of consciousness.

Pharmacology

Nuciferine has been reported to have various anti-inflammatory, possibly mediated via PPAR delta activation Nuciferine suppresses the SOX2-AKT/STAT3 signaling pathway in animal models. Targeting SOX-2 pathways in human models with Nuciferine may offer a novel therapeutic approach for cancer treatment.

According to a newer study from 2016, Nuciferine acts as an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B receptors, an inverse agonist at the 5-HT7 receptor, a partial agonist at D2, D5, and 5-HT6 receptors, and an agonist at 5-HT1A and D4 receptors. Additionally, it inhibits the dopamine transporter (DAT).

In rodent models relating to antipsychotic drug effects, Nuciferine has shown various actions such as blocking head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, enhancing amphetamine-induced locomotor activity, inhibiting phencyclidine (PCP)-induced locomotor activity, and restoring PCP-induced disruption of pre-pulse inhibition without inducing catalepsy.

Nuciferine may also potentiate morphine analgesia. The median lethal dose in mice is 289 mg/kg. It is structurally related to apomorphine and other aporphine derivatives.

References

^ Seligman, Sian (2023-01-13). "Blue Lotus Flower: Smoking, Tea & More". DoubleBlind Mag. Retrieved 2023-01-19.
^ Farrell, Martilias S.; McCorvy, John D.; Huang, Xi-Ping; Urban, Daniel J.; White, Kate L.; Giguere, Patrick M.; Doak, Allison K.; Bernstein, Alison I.; Stout, Kristen A.; Park, Su Mi; Rodriguiz, Ramona M.; Gray, Bradley W.; Hyatt, William S.; Norwood, Andrew P.; Webster, Kevin A. (2016). "In Vitro and In Vivo Characterization of the Alkaloid Nuciferine". PLOS ONE. 11 (3): e0150602. Bibcode:2016PLoSO..1150602F. doi:10.1371/journal.pone.0150602. ISSN 1932-6203. PMC 4786259. PMID 26963248.
^ a b c Bhattacharya, S. K.; Bose, R.; Ghosh, P.; Tripathi, V. J.; Ray, A. B.; Dasgupta, B. (1978-09-15). "Psychopharmacological studies on (--)-nuciferine and its Hofmann degradation product atherosperminine". Psychopharmacology. 59 (1): 29–33. doi:10.1007/bf00428026. ISSN 0033-3158. PMID 100809. S2CID 11847319.
^ Zhang, Lina; Gao, Jinghua; Tang, Peng; Chong, Li; Liu, Yue; Liu, Peng; Zhang, Xin; Chen, Li; Hou, Chen (October 2018). "Nuciferine inhibits LPS-induced inflammatory response in BV2 cells by activating PPAR-γ". International Immunopharmacology. 63: 9–13. doi:10.1016/j.intimp.2018.07.015. ISSN 1878-1705. PMID 30056259. S2CID 51894703.
^ Li, Zizhuo; Chen, Yaodong; An, Tingting; Liu, Pengfei; Zhu, Jiyuan; Yang, Haichao; Zhang, Wei; Dong, Tianxiu; Jiang, Jian; Zhang, Yu; Jiang, Maitao (2019-03-29). "Nuciferine inhibits the progression of glioblastoma by suppressing the SOX2-AKT/STAT3-Slug signaling pathway". Journal of Experimental & Clinical Cancer Research. 38 (1): 139. doi:10.1186/s13046-019-1134-y. ISSN 1756-9966. PMC 6440136. PMID 30922391.
^ a b Farrell, Martilias S.; McCorvy, John D.; Huang, Xi-Ping; Urban, Daniel J.; White, Kate L.; Giguere, Patrick M.; Doak, Allison K.; Bernstein, Alison I.; Stout, Kristen A.; Park, Su Mi; Rodriguiz, Ramona M.; Gray, Bradley W.; Hyatt, William S.; Norwood, Andrew P.; Webster, Kevin A. (2016-03-10). "In Vitro and In Vivo Characterization of the Alkaloid Nuciferine". PLOS ONE. 11 (3): e0150602. Bibcode:2016PLoSO..1150602F. doi:10.1371/journal.pone.0150602. ISSN 1932-6203. PMC 4786259. PMID 26963248.
^ Bhattacharya SK, Bose R, Ghosh P, Tripathi VJ, Ray AB, Dasgupta B (Sep 1978). "Psychopharmacological studies on (—)-nuciferine and its Hofmann degradation product atherosperminine". Psychopharmacology. 59 (1): 29–33. doi:10.1007/BF00428026. PMID 100809. S2CID 11847319.
^ Spess, David L. Errors in Alkaloids of Nelumbo and Nymphaea species, 2011, academia.edu