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, D. K. Lahiri

Research output: Contribution to journalArticle

2 Scopus citations

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 (US)
Pages (from-to)58-63
Number of pages6
JournalProgress in Nutrition
Volume12
Issue number1
StatePublished - Jun 29 2010

Keywords

  • Alzheimer's disease
  • Eserine
  • Physostigmine

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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    Greig, N. 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, D. K. (2010). From natural products to Alzheimer experimental therapeutics, eserine based drugs as symptomatic and disease altering agents. Progress in Nutrition, 12(1), 58-63.