Nuciferine is a 5-HT2A, 5-HT2C and 5-HT2B antagonist (inhibitor) with IC50 of 478 nM, 131 nM and 1 μM respectively; it is also an inverse agonist of 5-HT7 with IC50 of 150 nM.

Physicochemical Properties

Molecular Formula	C19H21NO2
Molecular Weight	295.3755
Exact Mass	295.157
CAS #	475-83-2
PubChem CID	10146
Appearance	White to off-white solid powder
Density	1.1±0.1 g/cm3
Boiling Point	430.7±45.0 °C at 760 mmHg
Melting Point	165.5°C
Flash Point	151.9±17.3 °C
Vapour Pressure	0.0±1.0 mmHg at 25°C
Index of Refraction	1.597
LogP	4.12
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	2
Heavy Atom Count	22
Complexity	401
Defined Atom Stereocenter Count	1
SMILES	O(C([H])([H])[H])C1=C(C([H])=C2C([H])([H])C([H])([H])N(C([H])([H])[H])[C@]3([H])C([H])([H])C4=C([H])C([H])=C([H])C([H])=C4C1=C32)OC([H])([H])[H]
InChi Key	ORJVQPIHKOARKV-OAHLLOKOSA-N
InChi Code	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
Chemical Name	(6aR)-1,2-dimethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Similar to aripiprazole (Emax=50% of dopamine), nuciferine is a partial agonist at the DD2 receptor with action (Emax=67% of dopamine). Nuciferine is as effective as clozapine (Nuciferine KB=62 nM; Clozapine KB=20 nM) at blocking Gi activation of dopamine inducers, which is consistent with its partial agonist action, according to Schild regression analysis [1]. Nuciferine, a naturally occurring substance, effectively inhibits the movement of insects. Schistosoma adenalis's basal motility and 5-HT-induced motility can both be successfully inhibited by nuciferine. Nuciferine inhibits Schistosoma at 0.62±0.22 μM and Sm.5HTRL at 0.24±0.04 μM, respectively [2].
ln Vivo	In dental animal models related to the effects of antipsychotic drugs, nuciferine expands the apical response and prestimulatory effects of 5-HT2A agonists, replaces the precise stimulation of clozapine, enhances amphetamine-induced locomotor activity, and inhibits phencyclidine Piperidine (PCP)-induced locomotor activity and relieves PCP-induced prepulse inhibition but does not induce catalepsy. In the presence of 1 or 3 mg/kg Nuciferine, cumulative PCP dosages resulted in equivalent replacement to PCP alone. In clozapine-trained animals, a dose-dependent substitution of 1.25 mg/kg Clozapine was observed with 10 mg/kg Nuciferine (80.63% drug lever response), with an ED50 value of 5.42 mg/kg (95% CI 3.09-9.48 mg )/kg), whereas the lower doses tested (0.1 mg/kg-3 mg/kg) failed to produce discriminative cues for clozapine. In addition to eliciting a high number of responses to clozapine suitable levers, 10 mg/kg Nuciferine generated considerable gradient suppression (p<0.001) compared to vehicle control points [1].
References	[1]. Farrell MS, et al. In Vitro and In Vivo Characterization of the Alkaloid Nuciferine. PLoS One. 2016 Mar 10;11(3):e0150602. [2]. Chan JD, et al. Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist. Int J Parasitol Drugs Drug Resist. 2016 Dec;6(3):364-370
Additional Infomation	Nuciferine has been reported in Ziziphus jujuba, Paliurus hemsleyanus, and other organisms with data available.

Solubility Data

Solubility (In Vitro)

DMSO : ~5 mg/mL (~16.93 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.11 mg/mL (3.76 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 11.1 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.11 mg/mL (3.76 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 11.1 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.3855 mL	16.9273 mL	33.8547 mL
	5 mM	0.6771 mL	3.3855 mL	6.7709 mL
	10 mM	0.3385 mL	1.6927 mL	3.3855 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.