On Sat, 2 Feb 2002 12:35:31 +1000, "John H." <John at overhere> wrote:
>>So then, any ideas on how users might be able to raise Ach levels?
IAN: Good analysis. There are several over-the-counter (OTC)
supplements that probably raise acetylcholine. Almost any of
the supplement formulas, such as "Deep Thought" (KAL), have
some, such as choline. However, there is one OTC supplement
that is an extremely effective means to raise acetylcholine.
It is a chemical from Chinese moss called huperzine A, which
is a more potent acetylcholinesterase (ACE) inhibitor than the
prescription drugs for Alzheimer's, Cognex (tacrine) and Aricept
(donepezil). ACE is the chemical that breaks down acetylcholine.
ACE inhibitors increase acetylcholine in a similar fashion that
MOA inhibitors increase serotonin. The following is from a PubMed
search I did a couple years ago. Huperzine is consistently shown
to be *more* effective (and safer) than the prescription drugs
used to treat Alzheimer's by raising acetylcholine. The interest
of the medical establishment in huperzine is not to get this more
effective and safer drug to people, but how to develop patentable
new drugs based on understanding how and why huperzine is superior
while giving people less effective and less safe patented drugs in
the meantime. Huperzine is available in most health food stores.
http://IanGoddard.net
"To lengthen thy life, lessen thy meals." Benjamin Franklin
http://www.ultraHIQ.net/Ubiquity/Winter02/CR.html
Pharmacol Biochem Behav 1998 Jun;60(2):377-86:
"Oral huperzine A exhibited higher efficacy on the inhibition of
AChE in the cortex and hippocampus than those of E2020 and tacrine."
Eur J Pharmacol 1998 May 22;349(2-3):137-42:
"The compared data demonstrate that (-)-huperzine A is the most potent
and orally active acetylcholinesterase inhibitor of the three, and
fits more closely the established criterions for an ideal
acetylcholinesterase inhibitor to be used in clinical studies."
Neuroreport 1997 Mar 3;8(4):963-8:
"The data suggest that Huperzine A could be a potent neuroprotective
agent not only where cholinergic neurons are impaired, but also under
conditions in which glutamatergic functions are compromised."
Neuroreport 1995 Nov 13;6(16):2221-4:
"Huperzine A, a novel, potent, reversible, and selective
acetylcholinesterase (AChE) inhibitor has been expected to be superior
to other AChE inhibitors now for the treatment of memory deficits in
patients with Alzheimer's disease."
Fundam Clin Pharmacol 1997;11(5):387-94:
"In conclusion, HUP, unlike PYR, protects against soman-induced
convulsions and neuropathological changes in the hippocampus. This
efficacy seems to be related to a protection by HUP of both
peripheral and central stores of AChE."
===============================================================
Bioorg Med Chem Lett 1999 Aug 16;9(16):2335-8
Potent, easily synthesized huperzine A-tacrine hybrid
acetylcholinesterase inhibitors.
Carlier PR, Du DM, Han Y, Liu J, Pang YP
Department of Chemistry, Hong Kong University of Science and
Technology, Clear Water Bay, Kowloon. chpaul at ust.hk
Hybrid acetylcholinesterase inhibitors composed of a key fragment of
huperzine A and an intact tacrine unit were prepared. The syntheses
are quite direct, proceeding in a maximum of 4 linear steps from
commercially available starting materials. The optimum hybrid
inhibitor (+/-)-9g is 13-fold more potent than (-)-huperzine A, and
25-fold more potent than tacrine.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10476864&form=6&db=m&Dopt=b
=================================================================
Ann Pharm Fr 1999 Sep;57(5):363-73
[No title available].
[Article in French]
Pilotaz F, Masson P
Centre de Recherches du Service de Sante des Armees Emile Parde,
Departement de Toxicologie, La Tronche.
[Medline record in process]
Huperzine A is an alkaloid isolated from a chinese club-moss. The
molecule is a potent and selective inhibitor of acetylcholinesterase.
Several pharmacological and clinical studies showed that huperzine A
improves the mnesic capacity and cognitive functions. Huperzine A was
also found to be a neuroprotective agent. This molecule which
possesses a high pharmacological potential is under clinical
evaluation for the palliative treatment of Alzheimer's disease. In
addition, its use in the pretreatment of poisoning by
organophosphorous nerve agents could be another indication.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10520506&form=6&db=m&Dopt=b
================================================================
J Pharmacol Exp Ther 1999 Feb;288(2):814-9
Improving effects of huperzine A on spatial working memory in aged
monkeys and young adult monkeys with experimental cognitive
impairment.
Ye JW, Cai JX, Wang LM, Tang XC
State Key Laboratory of Drug Research, Shanghai Institute of Materia
Medica, Chinese Academy of Sciences, Shanghai, P.R. China.
Our previous studies demonstrated that huperzine A, a reversible and
selective acetylcholinesterase inhibitor, exerts beneficial effects on
memory deficits in various rodent models of amnesia. To extend the
antiamnesic action of huperzine A to nonhuman primates, huperzine A
was evaluated for its ability to reverse the deficits in spatial
memory produced by scopolamine in young adult monkeys or those that
are naturally occurring in aged monkeys using a delayed-response task.
Scopolamine, a muscarinic receptor antagonist, dose dependently
impaired performance with the highest dose (0.03 mg/kg, i.m.)
producing a significant reduction in choice accuracy in young adult
monkeys. The delayed performance changed from an average of 26.8/30
trials correct on saline control to an average of 20.2/30 trials
correct after scopolamine administration. Huperzine A (0.01-0. 1
mg/kg, i.m.) significantly reversed deficits induced by scopolamine
in young adult monkeys on a delayed-response task; performance after
an optimal dose (0.1 mg/kg) averaged 25.0/30 correct. In four aged
monkeys, huperzine A (0.001-0.01 mg/kg, i.m.) significantly increased
choice accuracy from 20.5/30 on saline control to 25.2/30 at the
optimal dose (0.001 mg/kg for two monkeys and 0.01 mg/kg for the other
two monkeys). The beneficial effects of huperzine A on
delayed-response performance were long lasting; monkeys remained
improved for about 24 h after a single injection of huperzine A. This
study extended the findings that huperzine A improves the mnemonic
performance requiring working memory in monkeys, and suggests that
huperzine A may be a promising agent for clinical therapy of cognitive
impairments in patients with Alzheimer's disease.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9918593&form=6&db=m&Dopt=b
=============================================================
Eur J Pharmacol 1998 May 22;349(2-3):137-42
Reversal of scopolamine-induced deficits in radial maze performance
by (-)-huperzine A: comparison with E2020 and tacrine.
Wang T, Tang XC
State Key Laboratory of Drug Research, Shanghai Institute of Materia
Medica,
Chinese Academy of Sciences.
The effects of (-)-huperzine A
((5R,9R,11E)-5-amino-11-ethylidene-5,6,9,10-
tetrahydro-7-methyl-5, 9-methanocycloocta[b]pyridin-2(1H)-one),
and of the hydrochloride salt of E2020
((R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)
-2-yl]-methyl piperidine) and tacrine
(9-amino-1,2,3,4-tetrahydroacridine),
on the scopolamine-induced memory deficits in rats were compared in a
radial maze, using a 4-out-of-8 baiting procedure. Scopolamine (0.15
mg/kg, i.p.) caused significant impairment in the rats' ability to
fulfil the radial maze task. (-)-Huperzine A (0.2-0.4 mg/kg, p.o.;
0.1-0.4 mg/kg, i.p.) had greater efficacy than E2020 (0.6-0.9 mg/kg,
p.o.; 0.3-0.6 mg/kg, i.p.) and tacrine (1.5-2.5 mg/kg, p.o.; 0.3-0.6
mg/kg, i.p.) on the improvement of scopolamine-induced working and
reference memory errors, respectively. There appeared to be an inverse
bell-shape dose-dependent effect for all three compounds tested. The
compared data demonstrate that (-)-huperzine A is the most potent and
orally active acetylcholinesterase inhibitor of the three, and fits
more closely the established criterions for an ideal
acetylcholinesterase inhibitor to be used in clinical studies.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9671090&form=6&db=m&Dopt=b
=============================================================
Pharmacol Biochem Behav 1998 Jun;60(2):377-86
Comparative studies of huperzine A, E2020, and tacrine on behavior and
cholinesterase activities.
Cheng DH, Tang XC
State Key Laboratory of Drug Research, Shanghai Institute of Materia
Medica, Chinese Academy of Sciences.
Comparative effects of cholinesterase inhibitors (ChEI) huperzine A
with E2020 and tacrine on the radial maze performance in ethylcholine
mustard aziridinium ion (AF64A)-treated rat and inhibition of
cholinesterase activity were studied. The intracerebroventricular
(i.c.v.) injection of AF64A (3 nmol/side) caused significant
impairment in the rat's ability to fulfill the partially baited maze
paradigm. Oral huperzine A (0.5-0.8 mg/kg), E2020 (1.0-2.0 mg/kg), and
tacrine (8.0 mg/kg) effectively reversed AF64A-induced working memory
deficit. The doses that improved AF64A-induced memory deficit were
correlated to about 25-30% (huperzine A) and less than 10% (E2020,
tacrine) inhibition of acetylcholinesterase (AChE) activity in the
cortex and hippocampus. Huperzine A, E2020 and tacrine all produced
dose-dependent inhibition of brain AChE following i.c.v. and oral
administration. Oral huperzine A exhibited higher efficacy on the
inhibition of AChE in the cortex and hippocampus than those of E2020
and tacrine. Tacrine was more effective in inhibiting plasma
butyrylcholinesterase (BuChE) than it was brain AChE. Conversely, the
BuChE activity was less affected by huperzine A and E2020. The results
showed that huperzine A had high bioavailability and more selective
inhibition on AChE activity in cortex and hippocampus. Huperzine A
fits more closely with the established criteria for an ideal AChE
inhibitor to be used in clinical studies.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9632220&form=6&db=m&Dopt=b
=============================================================
Fundam Clin Pharmacol 1997;11(5):387-94
Efficacy of huperzine in preventing soman-induced seizures,
neuropathological changes and lethality.
Lallement G, Veyret J, Masqueliez C, Aubriot S, Burckhart MF,
Baubichon D
Unite de Neurotoxicologie, CRSSA, La Tronche, France.
Huperzine A (HUP) is a potent reversible inhibitor of
acetylcholinesterase (AChE) that crosses the blood-brain barrier.
Its ability to prevent seizures and subsequent hippocampal
neuropathological changes induced by the organophosphate soman
was studied in guinea pigs. Results were compared to guinea pigs
treated with pyridostigmine (PYR, 0.2 mg/kg, subcutaneously). HUP
pretreatment at 0.5 mg/kg, intraperitoneally, totally prevented
seizures and ensured the survival of all animals for 24 h after
intoxication. Hippocampal tissue was then free of any neuronal damage.
Comparatively, all animals pretreated with PYR exhibited epileptic
activity after soman poisoning and five of six animals died.
Examination of the hippocampus of the only surviving guinea pig
pretreated with PYR showed extensive neuropathological changes.
Although HUP or PYR induced similar inhibitions of blood AChE
activity, only HUP pretreatment led to a decrease in central AChE
activity. In binding studies on guinea-pig brain homogenates, HUP had
no affinity for muscarinic, alpha-amino-3-hydroxy-5-methyl-4-isoxazole
propionic acid (AMPA) and gamma-aminobutyric acid (GABA)A receptors
and only a very low one for N-methyl-D-aspartate (NMDA) receptors.
In conclusion, HUP, unlike PYR, protects against soman-induced
convulsions and neuropathological changes in the hippocampus.
This efficacy seems to be related to a protection by HUP of both
peripheral and central stores of AChE.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9342591&form=6&db=m&Dopt=b
=============================================================
Chung Kuo Yao Li Hsueh Pao 1995 Sep;16(5):391-5
Efficacy of tablet huperzine-A on memory, cognition, and behavior in
Alzheimer's disease.
Xu SS, Gao ZX, Weng Z, Du ZM, Xu WA, Yang JS, Zhang ML, Tong ZH,
Fang YS, Chai XS, et al
Zhejiang Supervision and Detection Station of Drug Abuse, Zhejiang
Medical University, Hangzhou, China.
AIM: To evaluate the efficacy and safety of tablet huperzine-A (Hup)
in patients with Alzheimer's disease. METHODS: Using multicenter,
prospective, double-blind, parallel, placebo controlled and randomized
method, 50 patients were administered orally 0.2 mg (4 tablets) Hup
and 53 patients were given po 4 tablets of placebo bid for 8 wk. All
patients were evaluated with Wechsler memory scale, Hasegawa dementia
scale, mini-mental state examination scale, activity of daily living
scale, treatment emergency symptom scale, and measured with BP, HR,
ECG, EEG, ALT, AKP, BUN, Cr, Hb, WBC, and urine routine. RESULTS:
About 58% (29/50) of patients treated with Hup showed improvements
in their memory (P < 0.01), cognitive (P < 0.01), and behavioral (P <
0.01 functions. The efficacy of Hup was better than placebo (36%,
19/53) (P < 0.05). No severe side effect was found. CONCLUSION: Hup is
a promising drug for symptomatic treatment of Alzheimer's disease.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8701750&form=6&db=m&Dopt=b
================================================================
Neuroreport 1997 Mar 3;8(4):963-8
Huperzine A, a potential therapeutic agent for dementia, reduces
neuronal
cell death caused by glutamate.
Ved HS, Koenig ML, Dave JR, Doctor BP
Division of Biochemistry, Walter Reed Army Institute of Research,
Washington, DC 20307-5100, USA.
Huperzine a, a potential therapeutic agent for Alzheimer's disease,
inhibits acetylcholinesterase in primary cultures derived from
forebrain, hippocampus, cortex and cerebellum of embryonic rat brain.
Glutamate induces cell death in cultures from all these brain regions.
Maximum cell toxicity was observed in cerebellar cultures.
Pretreatment of cell cultures with Huperzine A reduced cell toxicity,
as evidenced by cytotoxicity assay and general morphology. Huperzine A
pretreatment also reduced glutamate-induced calcium mobilization, but
did not affect elevations in intraneuronal free Ca2+ ([Ca]i) caused by
KCl or (-)Bay K 8644. The data suggest that Huperzine A could be a
potent neuroprotective agent not only where cholinergic neurons are
impaired, but also under conditions in which glutamatergic functions
are compromised.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9141073&form=6&db=m&Dopt=b
==============================================================
Neuroreport 1996 Dec 20;8(1):97-101
Huperzine A, a novel promising acetylcholinesterase inhibitor.
Cheng DH, Ren H, Tang XC
State Key Laboratory of Drug Research, Shanghai Institute of Materia
Medica, Chinese Academy of Sciences, P.R. China.
The effects of huperzine A on memory impairments induced by
scopolamine were evaluated using a radial maze task and inhibition of
cholinesterase in vitro compared with the effects of E2020 and
tacrine. Scopolamine (0.2 mg kg-1) significantly impaired spatial
memory in rats. Huperzine A (0.1-0.4 mg kg-1, p.o.), E2020 (0.5-1.0 mg
kg-1, p.o.) and tacrine (1.0-2.0 mg kg-1, p.o.) could reverse these
scopolamine-induced memory deficits. The ratios of huperzine A, E2020
and tacrine for butyrylcholinesterase:acetylcholinesterase determined
by a colourimetric method were 884.57, 489.05, and 0.80, respectively.
The results demonstrated that huperzine A was the most selective
acetylcholinterase inhibitor, and improved the working memory deficit
induced by scopolamine significantly better than did E2020 or tacrine,
suggesting it may be a promising agent for clinical therapy of
cognitive impairment in patients with Alzheimer's Disease.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9051760&form=6&db=m&Dopt=b
==============================================================
Neuroreport 1995 Nov 13;6(16):2221-4
Huperzine A ameliorates the spatial working memory impairments induced
by AF64A.
Zhi QX, Yi FH, XI CT
Department of Pharmacology, Shanghai Institute of Materia Medica,
Chinese Academy of Sciences, People's Republic of China.
Huperzine A, a novel, potent, reversible, and selective
acetylcholinesterase (AChE) inhibitor has been expected to be superior
to other AChE inhibitors now for the treatment of memory deficits in
patients with Alzheimer's disease. We have assessed the effects of
huperzine A on performance of AF64A-treated rats in the radial maze.
AF64A (2 nmol per side, i.c.v.) caused significant impairment in rats'
ability to perform the spatial working memory task. This behavioural
impairment was associated with a significant decrease in the activity
of choline acetyltransferase (ChAT) in the hippocampus. Huperzine A
(0.4-0.5 mg kg-1, i.p.) significantly ameliorated the AF64A-induced
memory deficit. These results suggest that AF64A is a useful agent
for disrupting working memory processes by altering hippocampal
cholinergic function, and such impairment can be effectively
ameliorated
by huperzine A.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8595207&form=6&db=m&Dopt=b
============================================================
Pharmacol Biochem Behav 1995 Jun-Jul;51(2-3):415-9
Effect of huperzine A, a novel acetylcholinesterase inhibitor,
on radial maze performance in rats.
Xiong ZQ, Tang XC
Department of Pharmacology, Shanghai Institute of Materia Medica,
Chinese Academy of Sciences.
Rats were trained to run in a spatial, radial arm maze using a
procedure to determine two memory functions, working and reference
memory. The muscarinic antagonist, not the nicotinic antagonist,
impaired both working and reference memory of rats. Scopolamine
(0.125, 0.15, and 0.2 mg/kg, IP, 30 min before a session)
significantly impaired choice accuracy in the eight-arm maze. In
contrast, mecamylamine (5, 10, and 15 mg/kg) did not affect the
performance. Huperzine A (0.1, 0.2, and 0.3 mg/kg, IP, 30 min before
testing) and physostigmine (0.3 mg/kg, IP, 20 min before testing)
could reverse scopolamine-induced deficits in the task. Chronic
treatment with huperzine A (0.25 mg/kg, PO, once a day) for 8
consecutive days was as potent as acute treatment on attenuating
[blocking] the scopolamine-induced amnesia.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7667362&form=6&db=m&Dopt=b
===========================================================
J Ethnopharmacol 1994 Dec;44(3):147-55
Comparison of the effects of natural and synthetic huperzine-A on
rat brain cholinergic function in vitro and in vivo.
Tang XC, Kindel GH, Kozikowski AP, Hanin I
Department of Pharmacology, Shanghai Institute of Materia Medica,
Academia Sinica, China.
(-)-Huperzine-A has been shown to be a promising agent for the
treatment of dementia of the Alzheimer type. This substance is rare in
nature. We have been able to prepare a racemic mixture of
(+/-)-huperzine-A in quantity. In the absence of a chiral synthetic
procedure for (-)-huperzine-A, this study sought to determine whether
the racemic mixture would yield an in vitro and in vivo
pharmacological profile of activity similar to that of the natural
compound. The synthetic racemic mixture (+/-)-huperzine-A was 3 times
less potent than (-)-huperzine-A in vitro (IC50s of 3 x 10(-7) M and
10(-7) M, respectively) because the former consisted of a racemic
mixture of the compound in which the (+)-huperzine component was
considerably less potent (IC50 = 7 x 10(-6) M). A comparable magnitude
of effect was also observed in studies conducted in vivo, in which,
over a range of 0.1-2.0 mg/kg administeredintraperitoneally (i.p.),
both (-)-huperzine-A and (+/-)-huperzine-A exerted significant
inhibition of acetylcholinesterase activity, in all brain regions
tested (hippocampus, striatum, hypothalamus and frontal cortex).
This inhibition of acetylcholinesterase activity was inversely
related to levels of acetylcholine measured in the hippocampus and
followed the same time course of effect. (-)-Huperzine-A and
(+/-)-huperzine-A were shown to be more potent than physostigmine as
inhibitors of acetylcholinesterase in vitro (IC50 = 6 x 10(-7) M).
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7898122&form=6&db=m&Dopt=b
===================================================================
Chung Kuo Yao Li Hsueh Pao 1991 May;12(3):250-2
[Drug evaluation of huperzine A in the treatment of senile memory
disorders].
[Article in Chinese]
Zhang RW, Tang XC, Han YY, Sang GW, Zhang YD, Ma YX, Zhang CL, Yang RM
Zhejiang Academy of Medical Sciences, Hangzhou, China.
Huperzine A is an alkaloid which was first isolated from Huperzia
serrata (Thumb) Trev by Zhejiang Academy of Medical Sciences and
Shanghai Institute of Materia Medica, Chinese Academy of Sciences. It
exhibits a significant anticholinesterase activity and has been used
on myasthenia gravis patients. The therapeutic effects were studied by
random, match and double-blind method on 56 patients of multi-infarct
dementia or senile dementia and 104 patients of senile and presenile
simple memory disorders. The curative effects were evaluated by
Wechsler memory scale. The im dose for multi-infarct dementia was 0.05
mg bid for 4 wk, whereas that for senile and presenile simple memory
disorders was 0.03 mg bid for 2 wk. Saline was used on control group.
The result showed that the curative effect of huperzine A was
significant. Only a few patients felt slight dizziness and this did
not affect the therapeutic effects.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1781288&form=6&db=m&Dopt=b
==================================================================
Mem Inst Oswaldo Cruz 1991;86 Suppl 2:173-5
Development of natural products as drugs acting on central nervous
system.
Zhu XZ
Department of Pharmacology, Shanghai Institute of Materia Medica,
Chinese Academy of Sciences.
Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata
which was found to be a selective ChE inhibitor and could improve
learning and retrieval processes. Preliminary clinical studies showed
that Hup-A improve short- and long-term memory in patients of cerebral
arteriosclerosis with memory impairment.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1841995&form=6&db=m&Dopt=b
==================================================================
J Neurosci Res 1989 Oct;24(2):276-85
Effect of huperzine A, a new cholinesterase inhibitor, on the central
cholinergic system of the rat.
Tang XC, De Sarno P, Sugaya K, Giacobini E
Southern Illinois University School of Medicine, Department of
Pharmacology, Springfield 62794-9230.
The present study represents the first comprehensive investigation of
the effect of huperzine A (HUP-A), a new cholinesterase inhibitor
(ChEI) isolated from a Lycopodium species, upon acetylcholinesterase
(AChE) activity, acetylcholine (ACh) levels and release, and
cholinergic receptors in rat brain following acute i.m. or i.p.
administration. The study shows that HUP-A can produce a long-term
inhibition of AChE activity in brain (up to 360 min) and an increase
in the ACh levels up to 40% at 60 min. There is considerable regional
variation in the degree of ACh elevation after HUP-A with maximal
values seen in frontal (125%) and parietal (105%) cortex and smaller
increases (22-65%) in other brain regions. HUP-A at concentrations of
10(-6) to 10(-4) M does not significantly alter the electrically
evoked release of 3H-ACh from cortical slices. With the exception of
the highest concentrations (6 X 10(-4) M) the displacement effect of
HUP-A for cholinergic ligands is stronger for 3H-(-)nicotine than for
3H-QNB. A parallel autoradiographic study in the mouse shows that 60
min after i.v. injection (183 micrograms/kg) the drug is present in
all brain regions, but it is particularly concentrated in certain
areas such as frontoparietal cortex, nucleus accumbens, hippocampal,
and striatal cortex. Radio-activity is practically absent in the whole
body at 12 hr. Our study suggests that this new ChEI has interesting
cholinomimetic properties, and its effects satisfy more closely
established criteria for an ideal ChEI for therapeutic use than
previously tested compounds.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2585551&form=6&db=m&Dopt=bhttp://www.ncbi.nlm.nih.gov/PubMed/http://www.alzforum.org/members/research/drugs/HuperzineA.htmlhttp://IanGoddard.net
"To lengthen thy life, lessen thy meals." Benjamin Franklin
http://www.ultraHIQ.net/Ubiquity/Winter02/CR.html
