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Lycopodium Alkaloids: Pharmacology

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Abstract

The aim of this work is to review the current knowledge on the lycopodium alkaloids with an emphasis on their pharmacology and potential medical application. Lycopodium alkaloids are produced by club mosses, a vulnerable group of slow-growing lower plants. (−)-Huperzine A (hupA) isolated from Huperzia serrata is known for its potent and reversible acetylcholinesterase (AChE) inhibiting activity and is used as a drug for Alzheimer’s disease (AD) in China. In addition, hupA has been shown to have neuroprotective effects in preclinical studies. It is by far the most intensively studied lycopodium alkaloid and clinical trials do indicate positive effects on AD symptoms with minimum adverse effects. At present, the greatest hurdle for research and application of lycopodium alkaloids is the lack of sustainable methods to supply these compounds. Lycopodium alkaloids which resemble hupA in having favorable bioavailability, pharmacokinetics, and toxicological profiles, in addition to interesting biological activities, are likely to be included in the search for new drug leads in the future, for example, in the development of multi-target and multidrug therapies for AD and other neurodegenerative diseases.

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Abbreviations

Aβ:

Beta-amyloid

ACh:

Acetylcholine

AChE:

Acetylcholinesterase

AChEI:

Acetylcholinesterase inhibitor

AChR:

Acetylcholine receptor

AD:

Alzheimer’s disease

ADAS-Cog:

Alzheimer’s disease assessment scale – cognitive section

ADL:

Activities of daily living

BBB:

Blood brain barrier

b.i.d.:

Twice a day

BuChE:

Butyrylcholinesterase

BuChEI:

Butyrylcholinesterase inhibitor

ChE:

Cholinesterase

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

CYP:

Cytochrome P450

FDA:

Food and drug administration

hupA:

(−)-huperzine A

hupB:

(−)-huperzine B

i.m.:

Intramuscular

i.p.:

Intraperitoneal

i.v.:

Intravenous

MCI:

Mild cognitive impairment

MMSE:

Mini Mental State Examination

nAChR:

Nicotinic acetylcholine receptor

NGF:

Nerve growth factor

NIH:

National Institutes of Health

NMDA:

N-methyl D-aspartate

NOAEL:

No-observed-adverse-effect-levels

OP:

Organophosphate

p.o.:

Per os (oral)

s.c.:

Subcutaneous

TcAChE:

Torpedo californica acetylcholinesterase

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  1. Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hagi, Hofsvallagata 53, 107, Reykjavik, Iceland

    Prof. Elín Soffía Olafsdóttir, Elsa S. Halldorsdottir, N. M. Pich & S. Omarsdottir

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  1. Prof. Elín Soffía Olafsdóttir
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  2. Elsa S. Halldorsdottir
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  3. N. M. Pich
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  4. S. Omarsdottir
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Correspondence to Elín Soffía Olafsdóttir .

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Editors and Affiliations

  1. Botany Department, M.L. Sukhadia University, Durga Nursery Road, Udaipur, 313001, Rajasthan, India

    Kishan Gopal Ramawat

  2. Institute of Vine and Wine Sciences, Biological-Active Plant Substances Study, University of Bordeaux, 210 Chemin de Leysotte CS 50008, Villenave d'Ornon, 33882, France

    Jean-Michel Mérillon

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Olafsdóttir, E.S., Halldorsdottir, E.S., Pich, N.M., Omarsdottir, S. (2013). Lycopodium Alkaloids: Pharmacology. In: Ramawat, K., Mérillon, JM. (eds) Natural Products. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-22144-6_42

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