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HUPERZINE A

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Huperzine A, an alkaloid from the Chinese club moss Huperzia serrata, acts as a competitive, reversible acetylcholinesterase inhibitor with central and peripheral activity.

Specific Substances

    1) 5,9-Methanocycloocta(b)pyridin-2(1H)-one,
    2) 5-amino-11-ethylidene-5,6,9,10-tetrahydro-
    3) 7-methyl-,(5R-(5-alpha,9-beta,11E)-
    4) Huperzine) A
    5) Selagine
    6) HUP
    7) Molecular Formula: C15-H18-N2-O
    8) CAS 102518-79-6

Available Forms Sources

    A) FORMS
    1) Huperzine A is available in the United States, without a prescription, as 50 mcg capsules (Pepping, 2000).
    B) SOURCES
    1) Huperzine A is an alkaloid isolated from Huperzia serrata, a Chinese club moss (Pepping, 2000).
    2) Small amounts of huperzine A were found in Lycopodium selago, a fir club moss, following development of mild cholinergic symptoms in two people who consumed a tea containing Lycopodium selago (Felgenhauer et al, 2000).
    C) USES
    1) In China, huperzine A is approved for human use as a treatment of Alzheimer's disease, and in the United States, huperzine A is used as a dietary supplement for the correction of memory impairment (Lallement et al, 2002).
    2) For centuries, Huperzia serrata, from which huperzine A was isolated, was used as a Chinese herbal medicine for treatment of dementia, fever, inflammation, and to alleviate memory problems (S Budavari , 2001; Pepping, 2000).
    3) Huperzine A may be effective as prophylaxis against organophosphate nerve agent toxicity (Lallement et al, 2002; Patocka, 1998; Rocha et al, 1998; Grunwald et al, 1994).
    4) Huperzine A has shown broad spectrum insecticidal activity against the Australian carpet beetle (Anthrenocerus australis), the Australian sheep blowfly (Lucilia cuprina), and the webbing clothes moth (Tineola bisselliella) (Ainge et al, 2002).

Overview

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    B) Monitor vital signs and fluid and electrolyte levels in symptomatic patients.
    C) ATROPINE
    1) ATROPINE may be used to control cholinergic excess. Endpoint of therapy is drying of secretions. ADULT - Give 1 to 2 milligrams intravenously or intratracheally every five minutes as needed.
    2) PEDIATRIC - Give 0.02 milligram/kilogram intravenously, intratracheally or intraosseously, repeating every five minutes as needed.

Range Of Toxicity

    A) A specific minimum toxic dose has not been established.

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) Mild cholinergic effects have been reported, following therapeutic administration of huperzine A, and include bradycardia, hyperactivity, dizziness, nausea, vomiting, diarrhea, and anorexia. Hypertension was reported in two patients following consumption of a tea containing small amounts of huperzine A.
    B) WITH POISONING/EXPOSURE
    1) Overdose information was unavailable at the time of this review.
    0.2.7) NEUROLOGIC
    A) WITH THERAPEUTIC USE
    1) Hyperactivity, dizziness, and insomnia are mild cholinergic effects that may occur with huperzine A therapy. Slurred speech was reported following ingestion of a tea containing huperzine A.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) Mild cholinergic effects that have occurred with huperzine therapy include nausea, vomiting, diarrhea, abdominal pain, and anorexia.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Laboratory Monitoring

    A) Serum huperzine A levels are not clinically useful or readily available.
    B) Monitor vital signs and electrolyte levels in patients with severe vomiting or diarrhea.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) Mild cholinergic effects have been reported, following therapeutic administration of huperzine A, and include bradycardia, hyperactivity, dizziness, nausea, vomiting, diarrhea, and anorexia. Hypertension was reported in two patients following consumption of a tea containing small amounts of huperzine A.
    B) WITH POISONING/EXPOSURE
    1) Overdose information was unavailable at the time of this review.

Heent

    3.4.6) THROAT
    A) WITH THERAPEUTIC USE
    1) CIRCUMORAL PARESTHESIA - A 60-year-old woman developed numbness of the mouth approximately 2 hours after consuming 1 and 1/2 cups of tea containing fir club moss (Lycopodium selago). The patient recovered following decontamination with activated charcoal and supportive care (Felgenhauer et al, 2000). Laboratory analysis of the fir club moss revealed that it contained small amounts of huperzine A.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) BRADYCARDIA
    1) WITH THERAPEUTIC USE
    a) Bradycardia (47 bpm) was reported during an 8-week huperzine A efficacy trial (Pepping, 2000; Xu et al, 1995).
    B) HYPERTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) CASE REPORT - Two patients, a 62-year-old man and his 60-year-old wife, developed hypertension (systolic blood pressures of 200 mmHg and 185 mmHg, respectively) approximately 2 hours after drinking a tea that contained Lycopodium selago, a fir club moss. Laboratory analysis of the fir club moss revealed that it contained small amounts of huperzine A. Both patients recovered following decontamination with activated charcoal and supportive treatment (Felgenhauer et al, 2000).

Neurologic

    3.7.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hyperactivity, dizziness, and insomnia are mild cholinergic effects that may occur with huperzine A therapy. Slurred speech was reported following ingestion of a tea containing huperzine A.
    3.7.2) CLINICAL EFFECTS
    A) HYPERACTIVE BEHAVIOR
    1) WITH THERAPEUTIC USE
    a) Hyperactivity and dizziness were reported following therapeutic administration of huperzine A. Symptoms were thought to be due to a cholinergic mechanism (Pepping, 2000; Felgenhauer et al, 2000; Xu et al, 1995).
    b) INCIDENCE - During a huperzine A efficacy trial, hyperactivity occurred in 10% of patients (n=50) who received huperzine A as compared to 5.7% of patients (n=53) who received placebo (Xu et al, 1995).
    B) DISTURBANCE IN SPEECH
    1) WITH THERAPEUTIC USE
    a) CASE REPORT - Two patients drank a tea containing Lycopodium selago,a fir club moss, and developed slurred speech, as well as diaphoresis, vomiting, diarrhea, dizziness, hypertension, abdominal cramps, circumoral paresthesias, and myalgias. A laboratory analysis of the fir club moss revealed that it contained small amounts of huperzine A. The patients recovered following decontamination with activated charcoal and treatment with atropine, fluids, and electrolytes. The anticholinesterase activity of huperzine A isolated from the fir club moss showed a higher inhibitory potency than synthetic huperzine A (Felgenhauer et al, 2000).
    C) INSOMNIA
    1) WITH THERAPEUTIC USE
    a) INCIDENCE - Insomnia was reported as a cholinergic effect, during a huperzine efficacy trial, in 10% of patients (n=50) who ingested huperzine A as compared to 7.5% of patients (n=53) in the placebo group (Xu et al, 1995).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SEIZURES
    a) RATS - Facial-forelimb seizures were reported in rats following perfusion of huperzine A through a microdialysis probe into the cortex (Zhu & Giacobini, 1995).
    2) TWITCHING
    a) RATS - Fasciculations, splay of hind limbs, and tremor were observed in rats following intramuscular administration of huperzine A at a dose of 2 mg/kg (Tang et al, 1989); following intraperitoneal administration of huperzine A at doses of 0.3 to 0.5 mg/kg (Zhu & Giacobini, 1995); and following intravenous administration of huperzine A at doses of 0.5 to 2 mg/kg (Anon, 2000).
    3) SOMNOLENCE
    a) RATS - Intense sedation and a delay in the onset of normal EEG slow-wave sleep were reported in rats following intravenous administration of huperzine A at doses of 0.5 to 2 mg/kg (Anon, 2000).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Mild cholinergic effects that have occurred with huperzine therapy include nausea, vomiting, diarrhea, abdominal pain, and anorexia.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA, VOMITING AND DIARRHEA
    1) WITH THERAPEUTIC USE
    a) Nausea, vomiting, and diarrhea are common occurrences following therapeutic administration of huperzine A (Pepping, 2000; Xu et al, 1995).
    b) CASE REPORT - A 62-year-old man experienced repeated vomiting and diarrhea approximately 2 hours after consumption of a tea containing Lycopodium selago, a fir club moss. Laboratory analysis of the fir club moss revealed that it contained small amounts of huperzine A. The patient recovered following decontamination with activated charcoal and supportive care (Felgenhauer et al, 2000).
    B) ABDOMINAL PAIN
    1) WITH THERAPEUTIC USE
    a) CASE REPORT - A 60-year-old woman ingested 1 and 1/2 cups of tea containing fir club moss (Lycopodium selago) and, approximately 2 hours later, experienced abdominal cramps, as well as, hypertension, circumoral paresthesia, and slurred speech. The abdominal cramps completely resolved within 2 days after decontamination with activated charcoal (Felgenhauer et al, 2000). Laboratory analysis of the fir club moss revealed that it contained small amounts of huperzine A.
    C) LOSS OF APPETITE
    1) WITH THERAPEUTIC USE
    a) Anorexia has been reported as a cholinergic effect following therapeutic administration of huperzine A, occurring in 10% of patients (n=50) ingesting huperzine during a clinical trial as compared to 5.7% of patients (n=53) in the placebo group (Pepping, 2000; Xu et al, 1995).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) EXCESSIVE SWEATING
    1) WITH THERAPEUTIC USE
    a) CASE REPORT - A 62-year-old man experienced diaphoresis approximately 2 hours after consuming 1 and 1/2 cups of tea containing Lycopodium selago (fir club moss). The patient recovered following decontamination with activated charcoal and supportive care. Laboratory analysis of the fir club moss revealed that it contained small amounts of huperzine A (Felgenhauer et al, 2000).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE PAIN
    1) WITH THERAPEUTIC USE
    a) CASE REPORT - A 62-year-old man experienced cramps in his hands and legs approximately 2 hours after consuming 1 and 1/2 cups of tea containing fir club moss (Lycopodium selago). The patient spontaneously recovered 3 days later. Laboratory analysis of the fir club moss revealed that it contained small amounts of huperzine A (Felgenhauer et al, 2000).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Serum huperzine A levels are not clinically useful or readily available.
    B) Monitor vital signs and electrolyte levels in patients with severe vomiting or diarrhea.

Methods

    A) CHROMATOGRAPHY
    1) Reverse phase high pressure liquid chromatography was described for detection of huperzine A in human plasma. The minimal detection limit of huperzine A in plasma was 1.60 mcg/L (Qian et al, 1995).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Serum huperzine A levels are not clinically useful or readily available.
    B) Monitor vital signs and electrolyte levels in patients with severe vomiting or diarrhea.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) In case of huperzine A intoxication, treatment is primarily SYMPTOMATIC and SUPPORTIVE.
    B) MONITORING OF PATIENT
    1) Monitor vital signs in symptomatic patients.
    2) Monitor fluid and electrolyte levels in patients who develop severe vomiting.
    C) ATROPINE
    1) Atropine may be used to control cholinergic effects. The endpoint of therapy is usually the drying of secretions.
    2) ADULT - Give 1 to 2 milligrams intravenously or intratracheally every five minutes as needed.
    3) PEDIATRIC - Give 0.02 milligram/kilogram intravenously, intratracheally or intraosseously, repeating every five minutes as needed.

Range Of Toxicity

Summary

    A) A specific minimum toxic dose has not been established.

Therapeutic Dose

    7.2.1) ADULT
    A) ROUTE OF ADMINISTRATION
    1) ORAL -
    a) ALZHEIMER'S DISEASE - In clinical trials, the oral dose of huperzine A ranged from 50 to 200 micrograms twice daily (Pepping, 2000).
    2) INTRAMUSCULAR -
    a) MULTIFARCT/SENILE DEMENTIA - During a clinical trial conducted for determination of huperzine A efficacy, an intramuscular dose of 0.05 milligrams twice daily for 4 weeks resulted in a significant improvement of memory function (reviewed in Zhu & Giacobini, 1995).
    b) PRESENILE/SENILE MEMORY DISORDERS - During a clinical trial conducted for determination of huperzine A efficacy, an intramuscular dose of 0.03 milligrams twice daily for 2 weeks resulted in a significant improvement of memory function (reviewed in Zhu & Giacobini, 1995).
    7.2.2) PEDIATRIC
    A) GENERAL
    1) Clinical trials with the pediatric population were not available at the time of this review.

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 1793 mcg/kg (RTECS, 2002)
    2) LD50- (ORAL)MOUSE:
    a) 5200 mcg/kg (RTECS, 2002)
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 3 mg/kg (RTECS, 2002)
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 2472 mcg/kg (RTECS, 2002)
    5) LD50- (ORAL)RAT:
    a) 15 mg/kg (RTECS, 2002)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Huperzine A is a reversible inhibitor of acetylcholinesterase that prevents degradation of endogenous acetylcholine (Tang et al, 1989; Skolnick, 1997). Facilitating effects of Huperzine A on neuromuscular acetylcholine transmission are mediated through its anticholinesterase activity rather than any pre- or post-synaptic actions (Lin et al, 1997). Inhibition by Huperzine A is more specific for acetylcholinesterase which is more predominantly found in muscle and the nervous system than for butyrylcholinesterase which is primarily found in plasma (Saxena et al, 1997; Saxena et al, 1994). Huperzine A is more selective for acetylcholinesterase than tacrine or E2020 which are other cholinesterase inhibitors studied for use in Alzheimer's disease (Cheng et al, 1996).
    B) Huperzine A has actions and properties that may be beneficial in treating memory impairment in Alzheimer's disease. Huperzine A penetrates the brain where it produces a dose dependent increase in acetylcholine (Zhu & Giacobini, 1995).
    C) The specific action of Huperzine A on acetylcholinesterase makes it a promising antidote for organophosphate intoxication (Rocha et al, 1998).
    D) Pre-treatment of cells from various regions of rat brain with Huperzine A, reduced cell toxicity caused by glutamate. Huperzine A may be of benefit in Alzheimer's disease since glutamate-induced neuronal cell death is associated with this disease (Ved et al, 1997).

Physicochemical

Physical Characteristics

    A) Huperzine A is a white solid that is soluble in aqueous acids and CHCl(3) (Patocka, 1998).

Molecular Weight

    A) 242.32 (S Budavari , 2001)

References

General Bibliography

    1) Ainge GD, Lorimer ST, & Gerard PJ: Insecticidal activity of huperzine A from the New Zealand clubmoss, Lycopodium varium. J Agric Food Chem 2002; 50:491-494.
    2) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
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    4) Cheng DH, Ren H, & Tang XC: Huperzine A, a novel promising acetylcholinesterase inhibitor. NeuroReport 1996; 8:97-101.
    5) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    6) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    7) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    8) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    9) Felgenhauer N, Zilker T, & Worek F: Intoxication with huperzine A, a potent anticholinesterase found in the fir club moss. Clin Toxicol 2000; 38:803-808.
    10) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    11) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    12) Grunwald J, Raveh L, & Doctor BP: Huperzine A as a pretreatment candidate drug against nerve agent toxicity. Life Science 1994; 54:991-997.
    13) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    14) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    15) Lallement G, Baille V, & Baubichon D: Review of the value of huperzine as pretreatment of organophosphate poisoning. Neurotoxicol 2002; 23:1-5.
    16) Lin JH, Hu GY, & Tang XC: Comparison between huperzine A, tacrine, E2020 on cholinergic transmission at mouse neuromuscular junction in vitro. Acta Pharmacologica Sinica 1997; 18:6-10.
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    22) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    23) Rocha ES, Chebabo SR, & Santos MD: An analysis of low level doses of cholinesterase inhibitors in cultured neurons and hippocampal slices of rats. Drug Chem Toxicol 1998; 21:191-200.
    24) S Budavari : The Merck Index, 13th ed.(CD ROM version). Merck & Co, Inc. Whitehouse Station, NJ. 2001.
    25) Saxena A, Qian N, & Kovach IM: Identification of amino acid residues involved in the binding of huperzine A to cholinesterases. Protein Science 1994; 3:1770-1778.
    26) Saxena A, Redman AMG, & Jiang X: Differences in active site gorge dimensions of cholinesterases revealed by binding of inhibitors to human butyrylcholinesterase. Biochem 1997; 36:14642-14651.
    27) Skolnick AA: Old chinese herbal medicine used for fever yields possible new Alzheimer disease therapy. JAMA 1997; 277:776.
    28) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    29) Tang XC, De Sarno P, & Sugaya K: Effect of huperzine A, a new cholinesterase inhibitor, on the central cholinergic system of the rat. J Neurosci Res 1989; 24:276-285.
    30) Tang XC: Huperzine A (shuangyiping): a promising drug for Alzheimer's disease. Acta Pharmacologica Sinica 1996; 17:481-484.
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    32) Ved HS, Koenig ML, & Dave JR: Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate. NeuroReport 1997; 8:963-968.
    33) Xu SS, Gao ZX, & Weng Z: Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Acta Pharmacologica Sinica 1995; 16:391-395.