From natural products to Alzheimer experimental therapeutics, eserine based drugs as symptomatic and disease altering agents

Nigel H. Greig, R. E. Becker, Q. Yu, H. W. Holloway, D. Tweedie, W. Luo, T. Utsuki, D. K. Ingram, M. L. Maccecchini, J. T. Rogers, K. Sambamurti, Debomoy Lahiri

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Based on the hexahydropyrroloindole backbone of the natural product and alkaloid, (-)-physostigmine (eserine) - a short-acting non-selective reversible cholinesterase inhibitor, three series of compounds were designed and developed to overcome its pharmacokinetic and pharmacodynamic shortfalls to provide experimental therapeutics for Alzheimer's disease (AD) and pharmacological tools to define brain function in health, aging and disease. Posiphen and analogues are amyloid-β precursor protein (APP) and amyloid-β peptide (Aβ) lowering agents that are cholinergically inert but generate metabolites with anticholinesterase action. (-)-Bisnorcymserine and analogues are potent, centrally active, reversible, selective butyrylcholinesterase inhibitors, whereas (-)-phenserine and analogues are similar but selective acetylcholinesterase inhibitors, and each additionally lowers APP and Aβ generation as a secondary action. Defining the clinical value of these agents in AD and related dementias is a key focus of current research.

Original languageEnglish
Pages (from-to)58-63
Number of pages6
JournalProgress in Nutrition
Volume12
Issue number1
StatePublished - 2010

Fingerprint

Physostigmine
Cholinesterase Inhibitors
amyloid
Biological Products
Serum Amyloid A Protein
Amyloid beta-Protein Precursor
Alzheimer disease
drugs
therapeutics
Alzheimer Disease
physostigmine
cholinesterase inhibitors
Pharmaceutical Preparations
Butyrylcholinesterase
dementia
cholinesterase
pharmacology
acetylcholinesterase
Alkaloids
Amyloid

Keywords

  • Alzheimer's disease
  • Eserine
  • Physostigmine

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

From natural products to Alzheimer experimental therapeutics, eserine based drugs as symptomatic and disease altering agents. / Greig, Nigel H.; Becker, R. E.; Yu, Q.; Holloway, H. W.; Tweedie, D.; Luo, W.; Utsuki, T.; Ingram, D. K.; Maccecchini, M. L.; Rogers, J. T.; Sambamurti, K.; Lahiri, Debomoy.

In: Progress in Nutrition, Vol. 12, No. 1, 2010, p. 58-63.

Research output: Contribution to journalArticle

Greig, NH, Becker, RE, Yu, Q, Holloway, HW, Tweedie, D, Luo, W, Utsuki, T, Ingram, DK, Maccecchini, ML, Rogers, JT, Sambamurti, K & Lahiri, D 2010, 'From natural products to Alzheimer experimental therapeutics, eserine based drugs as symptomatic and disease altering agents', Progress in Nutrition, vol. 12, no. 1, pp. 58-63.
Greig, Nigel H. ; Becker, R. E. ; Yu, Q. ; Holloway, H. W. ; Tweedie, D. ; Luo, W. ; Utsuki, T. ; Ingram, D. K. ; Maccecchini, M. L. ; Rogers, J. T. ; Sambamurti, K. ; Lahiri, Debomoy. / From natural products to Alzheimer experimental therapeutics, eserine based drugs as symptomatic and disease altering agents. In: Progress in Nutrition. 2010 ; Vol. 12, No. 1. pp. 58-63.
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