Nantenine

Evid Based Complement Alternat Med. 2014;2014:580483.

Cytotoxicity of Aporphine, Protoberberine, and Protopine Alkaloids from Dicranostigma leptopodum (Maxim.) Fedde.[Pubmed: 24963327]

METHODS AND RESULTS:
Nine alkaloids with three different structural skeletons were isolated from Dicranostigma leptopodum (Maxim.) Fedde (Papaveraceae) by repeated silica gel column chromatography. Their chemical structures were identified on the basic of physicochemical and spectroscopic data. Among them, 10-O-methylhernovine (1), Nantenine (2), corytuberine (3), lagesianine A (4), and dihydrocryptopine (9) were first isolated from this plant.
CONCLUSIONS:
With a series of cytotoxic tests, compounds 2, 3, and 7 displayed cytotoxicity against SMMC-7721 with IC50 values of 70.08 ± 4.63, 73.22 ± 2.35, and 27.77 ± 2.29 μ M, respectively.

J Pharmacol Sci. 2011;115(2):254-7.

Biphasic tracheal relaxation induced by higenamine and nantenine from Nandina domestica Thunberg.[Pubmed: 21282929]

METHODS AND RESULTS:
We compared the effects of the extract from fruits of Nandina domestica Thunberg (NDE) and its constituents, higenamine and Nantenine, on contractile responses in isolated guinea-pig trachea. NDE (1 mg/ml) caused biphasic relaxation of the trachea precontracted with high-K(+) stimulation: the fast component was blocked by propranolol and mimicked by higenamine; and the slow was resistant to propranolol and mimicked by Nantenine. Ca(2+)-induced contraction under high-K(+) stimulation was antagonized by Nantenine or NDE + propranolol.
CONCLUSIONS:
These results suggest that NDE relaxes the trachea quickly through β-adrenoceptor stimulation by higenamine and slowly through Ca(2+) antagonism by Nantenine.

Eur J Pharmacol. 2003 Sep 5;477(1):53-8.

(+)-Nantenine isolated from Nandina domestica Thunb. inhibits adrenergic pressor responses in pithed rats.[Pubmed: 14512098]

The effects of (+)-Nantenine on various pressor responses, recently reported exerting competitive antagonistic activity at the alpha1-adrenoceptor/5-hydroxytryptamine (5-HT)2A receptor, were examined in vivo.
METHODS AND RESULTS:
(+)-Nantenine (0.03-3 mg/kg) caused a dose-dependent inhibition of the pressor response to phenylephrine (alpha1-adrenoceptor agonist) or 5-HT (5-HT receptor agonist) in both anesthetized and pithed rats. The pressor response to UK 14304 (5-Bromo-N-[2-imidazolin-2-yl]-6-quinoxalinamine) (an alpha2-adrenoceptor agonist) was inhibited by (+)-Nantenine (0.003-3 mg/kg) in pithed rats in a dose-dependent manner without affecting the angiotensin II-induced pressor response in anesthetized rats. The pressor response to sympathetic nerve stimulation was also inhibited by (+)-Nantenine (0.3-3 mg/kg) in a dose-dependent manner. (+)-Nantenine (3 mg/kg) facilitated the norepinephrine release induced by sympathetic nerve stimulation in pithed rats. In the guinea pig vas deferens, the initial component of contractions induced by electrical field stimulation was enhanced by (+)-Nantenine (1-30 microM) in a concentration-dependent manner, while the later component was inhibited by it.
CONCLUSIONS:
These data suggest that (+)-Nantenine has antagonistic activities on alpha1-adrenoceptors, alpha2-adrenoceptors and 5-HT2A receptors in pithed rats.

Phytomedicine. 2003;10(6-7):563-8.

Nantenine alkaloid presents anticonvulsant effect on two classical animal models.[Pubmed: 13678244 ]

The present study investigated the anticonvulsant and convulsant profiles of Nantenine, an aporphine alkaloid found in several vegetal species.
METHODS AND RESULTS:
At lower doses (20-50 mg/kg, i.p.) the alkaloid proved to be effective in inhibiting pentylenotetrazol- (PTZ 100 mg/kg, s.c.) and maximal electroshock-induced seizures (80 mA, 50 pulses/s, 0.2 s), suggesting its potential as an anticonvulsant drug. However, at higher doses (> or = 75 mg/kg, i.p.) a convulsant activity was observed.
CONCLUSIONS:
Comparing the present in vivo Nantenine effects on seizures with previous in vitro biphasic action on Na+, K+-ATPase activity, the convulsant effect appears to be related to inhibition of these phosphatase at high doses whereas anticonvulsant effect, observed at low doses, seems attributable to its stimulation and the resultant decrease of Ca2+-influx into the cell.

J Enzyme Inhib Med Chem. 2011 Feb;26(1):46-55.

Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations.[Pubmed: 20583856]

METHODS AND RESULTS:
Nantenine, as well as a number of flexible analogs, were evaluated for acetylcholinesterase (AChE) inhibitory activity in microplate spectrophotometric assays based on Ellman's method. It was found that the rigid aporphine core of Nantenine is an important structural requirement for its anticholinesterase activity. Nantenine showed mixed inhibition kinetics in enzyme assays. Molecular docking experiments suggest that Nantenine binds preferentially to the catalytic site of AChE but is also capable of interacting with the peripheral anionic site (PAS) of the enzyme, thus accounting for its mixed inhibition profile.
CONCLUSIONS:
The aporphine core of Nantenine may thus be a useful template for the design of novel PAS or dual-site AChE inhibitors. Inhibiting the PAS is desirable for prevention of aggregation of the amyloid peptide Aβ, a major causative factor in the progression of Alzheimer's disease (AD).

Psychopharmacology (Berl). 2004 May;173(3-4):270-7.

Nantenine: an antagonist of the behavioral and physiological effects of MDMA in mice.[Pubmed: 14740148 ]

No selective antagonists for the effects of MDMA have yet been identified. The structurally-similar, naturally-occurring plant alkaloid Nantenine (9,10-methylenedioxy-1,2 dimethoxyaporphine) may represent such a compound. To investigate the capacity of Nantenine to block and/or reverse MDMA-induced hyperthermia, lethality, locomotor stimulation, and head twitches in mice, and to compare these actions with those of the selective alpha1 antagonist prazosin and the selective 5-HT2A antagonist M100907.
METHODS AND RESULTS:
Pretreatments of either 10 mg/kg Nantenine or 1 mg/kg prazosin were administered 15 min before 32 mg/kg MDMA; core temperature and locomotor stimulation were then monitored via radiotelemetry for at least 3 h. In further hyperthermia studies, 32 mg/kg MDMA was administered first and temperature was allowed to rise for 30 min; 10 mg/kg Nantenine, 1 mg/kg prazosin, or 1 mg/kg M100907 was then administered in an attempt to reverse MDMA-induced hyperthermia. In lethality assays, percent lethality was quantified 2 h after MDMA injection in two distinct housing conditions, one or 12 mice per cage, with or without 15 min pretreatments of 10 mg/kg Nantenine or 1 mg/kg prazosin. Drug elicited head twitches were quantified for 10 min following administration of either MDMA enantiomer, with and without pretreatments of 1 mg/kg Nantenine, 0.1 mg/kg prazosin, or 0.001 mg/kg M100907. Nantenine blocked and rapidly reversed MDMA-induced hyperthermia, attenuated lethality in both housing conditions, and reduced MDMA-induced locomotor stimulation and head twitches in mice. Prazosin blocked, but did not reverse, MDMA-induced hyperthermia, attenuated lethality (more effectively in singly-housed animals), and reduced MDMA-induced locomotor stimulation and head twitches. M100907 did not reverse MDMA-induced hyperthermia, but effectively blocked drug-elicited head twitches.
CONCLUSIONS:
Nantenine functions as an effective antagonist against a wide range of MDMA-induced effects in mice. The antagonist actions of this compound at serotonin and adrenergic receptors may be differentially implicated across endpoints.

Bioorg Med Chem Lett. 2015 Sep 1;25(17):3451-4.

C4 phenyl aporphines with selective h5-HT(2B) receptor affinity.[Pubmed: 26227772]

METHODS AND RESULTS:
A group of aporphine alkaloids related to (±)-Nantenine (1) and bearing a C4 phenyl and various C1 or N-substituents, was synthesized and evaluated for affinity to h5-HT receptors. In general, unlike Nantenine, the analogs lack affinity for the h5-HT(2A) receptor and other 5-HT receptors but bind selectively to the h5-HT(2B) receptor. With regards to 5-HT(2B) affinity, there appears to be a low tolerance for bulky C1 or N-substituents when the C4 phenyl moiety is present.
CONCLUSIONS:
Compound 5a had the highest 5-HT(2B) affinity of the compounds tested, was found to be an antagonist and is selective vs other CNS receptors.

Nat Prod Res. 2014;28(15):1159-64.

A new alkaloid from the fruit of Nandina domestica Thunb.[Pubmed: 24897106 ]

METHODS AND RESULTS:
A new steroidal alkaloid, (20S,22R,24R)-24-ethyl-3-oxocholest-4-en-22-amino, named as nandsterine (1), together with 10 known alkaloids, palmatine (2), O-methylbulbocapnine (3), Nantenine (4), dehydroNantenine (5), glaucine (6), didehydroglaucine (7), dehydrocorydaline (8), jatrorrhizine (9), magnoflorine (10) and berberine (11), was isolated from the fruit of Nandina domestica Thunb. Their structures were elucidated by using spectroscopic methods as well as by comparing with the published data.
CONCLUSIONS:
Compound 1 was a new class of steroidal alkaloid isolated from the family Berberidaceae, meanwhile compounds 2, 3, 6-8 and 10 were obtained from N. domestica for the first time. Compound 1 exhibited cytotoxicity against HL-60 cells (human leukaemia) with IC50 values of 52.1 uM.