Huperzia serrata

Huperzine A/Drug Interactions:

  • AnalgesicsAnalgesics: In animal evidence, huperzine A induced antinociception (67).
  • AnticholinergicsAnticholinergics: The AChE inhibitory activity of huperzine A directly reversed the effects of atropine and scopolamine in animal models and in vivo (68; 69; 70).
  • Anticonvulsant agentsAnticonvulsant agents: According to secondary sources, based on animal evidence, huperzine A may reduce neuronal deaths induced by glutamate and protect mice from clonic seizures.
  • Beta-blockers (beta-adrenergic antagonists)Beta-blockers (beta-adrenergic antagonists): Huperzine A's peripheral cholinergic activity raises the theoretical possibility that it could diminish the effects of these common pulmonary and cardiovascular drugs (e.g., albuterol/salbutamol, terbutaline, isoproterenol, epinephrine), although there is no report of such effect. Huperzine A may have additive effects in the presence of beta-blockers (65).
  • Cardiovascular drugsCardiovascular drugs: Huperzine A may cause significant bradycardia (27). This has led to the caution that its effect may be additive with that of other drugs, such as beta-blockers and calcium channel blockers, that also cause bradycardia (65). Huperzine A reduced calcium currents through its N-methyl D-aspartate (NMDA) blocking action (71; 72), an observation that provides a theoretical basis for this concern. There is no direct experience in the human literature.
  • Cholinesterase inhibitorsCholinesterase inhibitors: In in vitro and in vivo evidence, huperzine A was a potent inhibitor of acetylcholinesterase (5; 30; 31; 32; 33; 34; 35).
  • Cytochrome P450: substrates, inhibitors, inducersCytochrome P450: substrates, inhibitors, inducers: Huperzine A appears to undergo hepatic metabolism primarily via cytochrome P450 1A2 and 3A1/2 mechanisms, which are shared by common drugs such as acetaminophen (phenacetin) (66).
  • Drugs that effect GABADrugs that effect GABA: The NMDA receptor-blocking effect of huperzine A raises the theoretical possibility of its interaction with other drugs that potentiate or inhibit that receptor's activity. In vivo evidence has demonstrated an additive effect of the NMDA receptor antagonist MK801 with benzodiazepines on reduction in induced convulsions in mice (73). Until more is known about the in vivo and human effects of huperzine A's NMDA-blocking activity, caution is indicated in its use in combination with benzodiazepines and other GABAergic drugs.
  • NMDA receptor antagonistsNMDA receptor antagonists: Memantine (Namenda?) is an NMDA antagonist licensed for use in Alzheimer's disease (74). Memantine could theoretically potentiate huperzine's NMDA-antagonist effects.
  • ScopolamineScopolamine: An animal study showed huperzine A to improve naturally occurring memory or memory loss induced by scopolamine in aged rats (75).

    • Huperzine A/Herb/Supplement Interactions:

  • AChE inhibitor herbs and supplementsAChE inhibitor herbs and supplements: Salvia lavandulaefolia Vahl (Spanish sage) essential oil and some of its monoterpenoid constituents are acetylcholinesterase (AChE) inhibitors (76).
  • AnalgesicsAnalgesics: According to animal evidence, huperzine A induced antinociception (67).
  • Anticholinergic herbsAnticholinergic herbs: Natural belladonna compounds containing the alkaloids atropine, scopolamine, and hyoscyamine are in widespread use for a variety of indications, with varying degrees of evidence (77). Huperzine A's AChE inhibition will antagonize the anticholinergic effects of belladonna.
  • AnticonvulsantsAnticonvulsants: According to secondary sources, based on animal evidence, huperzine A reduced neuronal deaths induced by glutamates and protects mice from clonic seizures.
  • AntioxidantsAntioxidants: According to in vitro evidence, huperzine A protected against hydrogen peroxide-induced injury in rat pheochromocytoma cells (78; 79) and inhibited nitric oxide production from rat C6 astrocytoma cells (80).
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: Stephania extracts contain the agent fangchinoline, which blocks Ca+2 currents in vitro (81). Polygalae radix (PR) from Polygala tenuifolia (Polygalaceae) is traditionally used in China and Korea as a sedative, anti-inflammatory, and antibacterial agent. It has been shown to reduce Ca+2 currents in vitro (82). These findings suggest the theoretical possibility of potentiation of action between these agents and huperzine A, which also reduces calcium currents through its NMDA blockade (71; 72).
  • Cytochrome P450: substrates, inhibitors, inducersCytochrome P450: substrates, inhibitors, inducers: Huperzine A appears to undergo hepatic metabolism primarily via cytochrome P450 1A2 and 3A1/2 mechanisms, which are shared by common drugs such as acetaminophen (phenacetin) (66).
  • Ginkgo bilobaGinkgo biloba: Concomitant use of huperzine A with Ginkgo biloba may lead to altered pharmacological properties of each product (anecdotally). Bilobalide, an extract of G. biloba, also has weak NMDA-blocking activity (83).
  • NMDA-blocking herbs and supplementsNMDA-blocking herbs and supplements: A large number of natural supplements and extracts contain one or more agents that function as NMDA blockers and that could theoretically potentiate the NMDA blockade by huperzine A. These agents include linalool (found in cinnamon and other essential oil extracts) (84), aqueous extracts from rhizomes of Cyperus articulatus (85), aqueous extracts of Scutellaria baicalensis, Stephania tetrandra, Salvia miltiorrhiza, Uncaria rhynchophylla (Choto-san, Chotoko) (86; 87), and Tianmacuzhi granules (88). Because these preparations have applications for stroke and other brain dysfunctions in traditional Chinese medicine, there is the strong likelihood that patients using huperzine A may also be using one or more of these other agents.
  • ScopolamineScopolamine: An animal study showed huperzine A to improve naturally occurring memory or memory loss induced by scopolamine in aged rats (75).

    • Huperzine A/Food Interactions:

  • Insufficient available evidence.

    • Huperzine A/Lab Interactions:

  • Liver enzymesLiver enzymes: In an in vivo rat model, huperzine A caused elevation of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a fashion independent of hepatotoxicity (36). There are no human data on huperzine's effect on transaminase levels or measurement.