Summary of Higenamine
Primary Information, Benefits, Effects, and Important Facts
Higenamine is a molecule derived from a variety of fruits and plants that appears to have anti-asthmatic properties via dilating the bronchial tubes (a mechanism known as Beta(2)adrenergic agonism). This mechanism is also the same one underlying the fat burning potential of ephedrine, and as such Higenamine is currently being used as a fat burner.
Currently, there is no human evidence using Higenamine and it appears to be similarly potent to some established beta(2)adrenergic agonists in preliminary studies (in regards to anti-asthmatic effects).
Beyond that mechanism, it may also exert anti-inflammatory effects and injections may be useful in a clinical setting against sepsis.
Higenamine is on the FDA's Dietary Supplement Ingredient Advisory List as of April, 2019. These are ingredients that do not appear to be lawful ingredients in dietary supplements. The list is subject to change (check the provided link for current status).
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Frequently Asked Questions about Higenamine
Scientific Research on Higenamine
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Higenamine (Norcoclaurine) is a benzyltetrahydroisoquinoline  that is found in a variety of plants, and seems to be in relatively high concentrations in the fruits of Nandina domestica Thunberg of the Berberidaceae family.
Known plants to possess a Higenamine content are:
Argemone mexicana 
Magnolia salicifolia 
Tinospora crispa 
Coptis japonica 
A constituent of a variety of plants, rather than a single isolated plant
Higenamine, also known as norcoclaurine, is known as a benzyltetrahydroisoquinoline. 
It is found in ethanol extracts of the plant rather than water extracts alongside the related compound Nantenine.  When the extract was divided into 12 sub fragments to isolate the plant compounds, the fragment that contained higenamine (at 49%) was as potent as the plant itself on tracheal relaxation.  Despite the ethanol extract above, the structure is highly polar. Higenamine is unstable in basic solution,  and has a molecular weight of 271.31g/mol.
Following an IV injection of Higenamine in healthy volunteers at 0.5-4mcg/mL/min (total doses of 0.2, 4, and 40ng/mL), the AUC was determined to be 5.39ng/h/mL with a half-life of 0.133 hours, and 9.3% of the injected solution was found in the urine after 8 hours.  This study is duplicated in Medline,  and a similarly short half life has been noted in rabbits either injected or fed Higenamine (50mg/kg bodyweight).  
The only oral study currently conducted is in rabbits, where 50mg/kg showed high variance in bioavailability and serum concentrations despite hitting similar Tmax values 7.8-8.3 minutes after gastric intubation.  
When divided into two apparently different groups, the bioavailability was either 2.84+/-0.82% or 21.86+/-2.21% and the serum Cmax values of these groups were (respectively) 0.33+/-0.09mcg/mL and 2.90+/-0.51mcg/mL; both groups attenuating to 20ng/mL after 2 hours.   These values are for total Higenamine, and serum binding to protein appears to hold static at around 54.8%,   and an injection of 20mg/kg Higenamine to rabbits appears to correlate very well to oral administration of 50mg/kg.   
Differences in serum values may be mediated at the level of either intestinal absorption or conjugation, and the main conjugative metabolite appears to be via glucuronidation (as assessed by urinary recovery).  
Minimal pharmacokinetic data at this moment in time, but Higenamine appears to exert a very rapid absorption phase with a very rapid half-life as well. There appears to be a degree of inter-individual difference in how much Higenamine gets into the blood, which may be mediated by Glucuronidation enzymes (possible synergism with Piperidine from Black Pepper if this is the case)
The EC50 value of Higenamine in trachea cells is 47.6+/-1.8ng/mL when looking at a fragment of 49% higenamine extracted from Nandina.  although a molar value of 86.0+/-3.3nM was found when looking at Higenamine in isolation; giving Higenamine itself an EC50 of 23.33ng/mL.  Synthetic Higenamine appears to have slightly higher EC50 than does that derived from Nandina. 
The IC50 value on RAW 264.7 cells (an experimental mouse line of leukocyte immune cells) was 53uM after a 10mg/kg bodyweight I.P injection. 
A concentration of 10uM Higenamine in motor neurons isolated form mice (in vitro study) appear to enhance acetylcholine release, and are blocked by propanolol (thus mediated via Beta(2)adrenergic agonism, a known mechanism of Higenamine).  Concentrations of 30-100uM Higenamine diminished the ability of motor neurons to release acetylcholine when stimulated, suggesting peak efficacy in the 10-30uM range.  Spontaneous release of acetylcholine (without nerve stimulation) was slightly increased.
Possesses possible benefits to muscular output (via increasing acetylcholine release from motor neurons), but no in vivo evidence to assess potency nor optimal dose; mechanism is via beta(2)adrenergic activation
At a concentration of 20mM, Higenamine has been shown in vitro to deplete dopamine concentrations in PC12 neuronal cells by 55.2% with an IC50 of 18.2mM;  this was thought to be through inhibition of tyrosine hydroxylase, which converts L-DOPA into dopamine. 
May inhibit tyrosine hydroxylase and suppress dopamine, but no in vivo evidence exists
In a rat model of MCAO injury (middle cerebral artery occlusion), 10mg/kg Higenamine (not disclosed whether oral or intracerebral) significantly reduce the infarct size suggesting neuroprotective effects under periods of ischemia. 
In vitro, it appears Higenamine increases cell viability in a concentration dependent manner up to 10uM where it stabilizes (higher concentrations not being more effective) which may have been secondary to Higenamine inducing expression of HO-1 (Heme-Oxygenase 1; an anti-oxidant protein which downregulates the proinflammatory HMGB1) at concentrations of 10uM or higher in normoxia and only requiring 1uM in periods of hypoxia.  In C6 cells (glial cells), Higenamine induced phosphorylation of PI3K/Akt in a concentration dependent manner which was causative of this increase in HO-1 vicariously through activation of Nrf2. 
Induction of HO-1 also appears to be the mechanism underlying protection against myocardial ischemia-reperfusion from Higenamine. 
Higenamine appears to be protective under instances of Ischemia (lack of oxygen), with the exact mechanisms known but not yet compared to an active control (to assess potency of these protective effects)
In serum isolated from rats and humans, Higenamine appears to have antiplatelet aggregating propeties with an IC50 value of 140uM in response to Arachidonic Acid (AA) induced clotting, noted to be half as effective as Aspirin (used as an active control), but against U46619-induced aggregation Higenamine (73uM IC50) was more effective than Aspirin on rat platelets  and show efficacy on collagen and ephinephrine-induced aggregation as well.  Higenamine may directly compete at TA receptors (Arachidonic acid metabolizes to Thromboxane A2 and acts on these receptors to induce platelet aggregation  ) since it seems fairly weak at actually suppressing Arachidonic Acid metabolism into Thromboxane A(2) with an IC50 2990uM.  Anti-thrombotic effects have been observed in mouse acute thrombosis model and rat AV shunt models after oral ingestion of 50-100mg/kg bodyweight  and after oral administration of 10-50mg/kg Higenamine in a rat model of disseiminated intravascular coagulation;  the S-Enantiomer may be more potent than the R-enantiomer of Higenamine,  but the previous studies used a racemic mixture of the two.
Higenamine per se appears to have anti-thrombotic potential, which seems to be related to competing with Thromboxane A(2) at the receptor level. These have been noted at oral intakes of 50-100mg in rats (8-16mg in humans)
Higenamine can increase the rate and force of contraction of the heart with EC50 values of 38nM and 97nM respectively, with the maximal response (3uM) being comparable to isoproterenol (100nM) although on the EC50 basis it was 20-fold less potent.  This positive chronotropic response to Higenamine was via activation of the adrenergic B1 receptors, and submaximal concentrations of Higenamine (2.5nM) that per se do not influence contractile rate can augment Aconitate-induced contractile rate secondary to B1 agonism. 
A positive ionotropic effect of Higenamine also exists with an EC50 of 97nM (95% CI of 81.5-115.2nM), again being approximately 20-fold less potent than isoproterenol. 
Has the same mechanisms as other beta adrenergic agonists to increase heart rate; the oral dose required for this is not currently known
Higenamine is known as a Beta-adrenergic receptor agonist, a mechanism shared by ephedrine and synephrine for their ability to reduce fat mass. These effects appears to be wide-reaching affecting intestinal tissue,  bronchiol tissue (where it acts as a vasodilator),  cardiac tissue (atria   and ventricles  ). It appears to act on both the Beta(1) and Beta(2) subunit, with the Beta(3) subunit unexplored.
Possesses the same mechanisms as other stimulant fat burners to induce fat loss, but currently no evidnce exists to suggest potency of these effects in vivo
Higenamine is able to inhibit LPS-induced nitrite accumulation in macrophages, with an IC50 value of 53.4+/-2.6μM; this measurement for the racemic mixture was mostly due to S-Higenamine with an IC50 of 26.2+/-7.6μM (R-Higenamine with a value of 6, 86.3+/-5.4μM).  Reductions in the inflammatory response in isolated macrophages have been replicated elsewhere with similar potency to tetrandrin at the same concentration (0.01mM). 
A subsequent injection of 10mg/kg of the S-enantiomer reduced serum nitric oxide (induced by exposure to endotoxin) from 88+/-7μM to 28+/-5μM (68% decrease), with some efficacy from the racemic mixture and a higher dose of 20mg/kg being required for the weaker R-enantiomer.  These effects may be downstream of Higenamine reducing induction of iNOS (IC50 53+/-2.6μM) via NF-kB inhibition,  and decreases in serum nitric oxide (elevated during shock) replicated  and possibly secondary to NF-kB inhibition. 
Appears to possess anti-inflammatory mechanisms and may be useful in clinical settings for septic shock
Higenamine was found secondary to the fruits of Nandina domestica, which are a tradional asthmatic medication, to act on beta(2)adrenergic recpetors; the same receptor class that ephedrine and synephrine act upon.  The anti-asthmatic effects of Higenamine are wholly mediated via this receptor,   and activation of the beta(2)adrenergic receptor is anti-asthmatic in nature due to inducing bronchiol dilation (widening of breathing tubes). It should be noted that usage of Nandina domestica for anti-asthmatic effects may be more effective than Higenamine in isolation due to nantenine, another bioactive that has anti-asthmatic effects. 
When guinea pigs are exposed to histamine who were pretreated with test drugs, Higenamine was able to delay bronchiol convulsion by 1.7-fold relative to control (slightly underperforming salbuterol as active control, which exerted a 2.3-fold delay over control).  The benefit was dose dependent, and a higher concentration of Higenamine was more effective.
Nandina domestica has a long history of being helpful for asthmatics, and Higenamine is thought to contribute benficially. No actual interventions in living creatures exist aside from one Hamster study, suggesting similar potency to Salbuterol
In a study where low doses of Higenamine were injected into the rat penis (to avoid circulation and to better assess penile physiology), 0.0005mg/kg to 0.002mg/kg Higenamine increased relaxation of the corpus cavernosum in a dose-dependent manner with 1mM inducing 92.5+/-6.9% relaxation.  This relaxation was attenuated with propanolol, and thus was mediated via Beta(2)adrenergic agonsitic properties; and increased both cAMP and cGMP in a concentration dependent manner. 
Pre-treatment of rat corpus cavernosums with Higenamine enhanced the relaxation effects of PDE5 inhibitors, suggesting possible additive or synergistic effects. 
Appears to be proerectile, but no studies exist to connect the one rat study (injections) to oral dosing; may be synergistic with PDE5 inhibitors (Horny Goat Weed, Sophora Flavescens, Viagra)
A study cited in this paper  but otherwise inaccessible, from the journal Zhongguo Lin Chuang Yao Li Xue Za Zhi (Y.R Du et al.) suggests that the highest safe/recommended dose in humans is 24mcg/kg bodyweight as higenamine hydrochloride. Rabbit studies appear to use 50mg/kg acutely with no harm acutely (correlates to 11mg/kg) but no long term studies have been conducted.
Limited safety evidence on Higenamine
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