Higenamine (norcoclaurine) is a chemical compound found in a variety of plants including Nandina domestica (fruit), Aconitum carmichaelii (root), Asarum heterotropioides, Galium divaricatum (stem and vine), Annona squamosa, and Nelumbo nucifera (lotus seeds).
Pharmacology
Since higenamine is present in plants which have a history of use in traditional medicine, the pharmacology of this compound has attracted scientific interest. A variety of effects have been observed in in vitro studies and in animal models, but its effects in humans are unknown.
The results of a 2009 study exposed the compound as a beta-2 adrenergic receptor agonist.
In animal models, higenamine has been demonstrated to be a beta-2 adrenergic receptor agonist. Adrenergic receptors, or adrenoceptors, belong to the class of G-protein coupled receptors, and are the most prominent receptors in the adipose membrane, besides also being expressed in skeletal muscle tissue. These adipose-membrane receptors are classified as either alpha- or beta-adrenoceptors. Although these adrenoceptors share the same messenger, cyclic adenosine monophosphate (cAMP), the specific transduction pathway depends on the receptor type (alpha or beta). Higenamine partly exerts its actions by the activation of an enzyme, adenylate cyclase, responsible for boosting the cellular concentrations of the adrenergic second messenger, cAMP.
In a rodent model, it was found that higenamine produced cardiotonic, vascular relaxation, and bronchodilator effects. In particular, higenamine, via a beta-adrenoceptor mechanism, induced relaxation in rat corpus cavernosum, leading to improved vasodilation and erectile function.
Related to improved vasodilatory signals, higenamine has been shown in animal models to possess anti-platelet and antithrombotic activity via a cAMP-dependent pathway, suggesting higenamine may contribute to enhanced vasodilation and arterial integrity.
Toxicity
Regarding toxicity, researchers have suggested that the levels of higenamine reported in food consumption (estimated 47.5Â mg in a 9-ounce serving of Lotus) would be comparable to the amount used in food supplements. Higenamine is a beta-adrenergic agonist which has effects on the function of trachea and heart muscles. During a study of acute toxicity, mice were orally administered the compound at a dose of 2 g per kg of bodyweight. No mice died during the study. The serious heart-related side effects, including arrhythmias and even death, of aconite consumption may be caused by higenamine.