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Lycopodium Alkaloids: Pharmacology

  • Elín Soffía Olafsdóttir
  • Elsa S. Halldorsdottir
  • N. M. Pich
  • S. Omarsdottir
Reference work entry

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.

Keywords

Acetylcholinesterase Alzheimer’s disease biological activity clinical trials club mosses huperzine A Lycopodiaceae lycopodium alkaloids pharmacology 

Abbreviations

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Elín Soffía Olafsdóttir
    • 1
  • Elsa S. Halldorsdottir
    • 1
  • N. M. Pich
    • 1
  • S. Omarsdottir
    • 1
  1. 1.Faculty of Pharmaceutical Sciences, School of Health SciencesUniversity of IcelandReykjavikIceland

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