PMID- 15974893
OWN - NLM
STAT- MEDLINE
DCOM- 20051003
LR  - 20220318
IS  - 1567-2050 (Print)
IS  - 1567-2050 (Linking)
VI  - 2
IP  - 3
DP  - 2005 Jul
TI  - An overview of phenserine tartrate, a novel acetylcholinesterase inhibitor for 
      the treatment of Alzheimer's disease.
PG  - 281-90
AB  - Existing cholinesterase (ChE) inhibitor therapies for Alzheimer's disease (AD), 
      while effective in improving cognitive, behavioral and functional impairments, do 
      not alter disease progression. Novel drug design studies have focused on the 
      classical ChE inhibitor, (-)-physostigmine, producing alterations in chemical 
      composition and three-dimensional structure, which may offer an improved 
      therapeutic index. The phenylcarbamate derivative, (-)-phenserine, is a 
      selective, non-competitive inhibitor of acetylcholinesterase (AChE). In vivo, 
      (-)-phenserine produces rapid, potent, and long-lasting AChE inhibition. As a 
      possible result of its preferential brain selectivity, (-)-phenserine is 
      significantly less toxic than (-)-physostigmine. In studies using the Stone maze 
      paradigm, (-)-phenserine has been shown to improve cognitive performance in both 
      young learning-impaired and elderly rats. In addition to reducing inactivation of 
      acetylcholine in the brain, (-)-phenserine appears to have a second mode of 
      action. Reduced secretion of beta-amyloid (Abeta) has been observed in cell lines 
      exposed to (-)-phenserine, occurring through translational regulation of 
      beta-amyloid precursor protein (beta-APP) mRNA via a non-cholinergic mechanism. 
      These in vitro findings appear to translate in vivo into animal models and 
      humans. In a small study of patients with AD, (-)-phenserine treatment tended to 
      reduce beta-APP and Abeta levels in plasma samples. Clinical studies also reveal 
      that (-)-phenserine (5-10 mg b.i.d.) had a favorable safety and pharmacological 
      profile, produced significant improvements in cognitive function and was well 
      tolerated in patients with AD treated for 12 weeks. Further randomized, 
      double-blind, placebo-controlled Phase III studies assessing the efficacy, 
      safety/tolerability and potential disease-modifying effects of (-)-phenserine in 
      patients with AD are currently ongoing.
FAU - Greig, Nigel H
AU  - Greig NH
AD  - Drug Design & Development Section, Laboratory of Neurosciences, Intramural 
      Research Program, National Institute on Aging, National Institutes of Health, 
      Baltimore, MD 21224, USA. Greign@grc.nia.nih.gov
FAU - Sambamurti, Kumar
AU  - Sambamurti K
FAU - Yu, Qian-sheng
AU  - Yu QS
FAU - Brossi, Arnold
AU  - Brossi A
FAU - Bruinsma, Gosse B
AU  - Bruinsma GB
FAU - Lahiri, Debomoy K
AU  - Lahiri DK
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United Arab Emirates
TA  - Curr Alzheimer Res
JT  - Current Alzheimer research
JID - 101208441
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Tartrates)
RN  - 9U1VM840SP (Physostigmine)
RN  - SUE285UG3S (phenserine)
SB  - IM
MH  - Alzheimer Disease/*drug therapy
MH  - Animals
MH  - Cholinesterase Inhibitors/adverse effects/chemistry/pharmacokinetics/*therapeutic 
      use
MH  - Humans
MH  - Physostigmine/adverse effects/*analogs & 
      derivatives/chemistry/pharmacokinetics/therapeutic use
MH  - Tartrates/chemistry
RF  - 62
EDAT- 2005/06/25 09:00
MHDA- 2005/10/04 09:00
CRDT- 2005/06/25 09:00
PHST- 2005/06/25 09:00 [pubmed]
PHST- 2005/10/04 09:00 [medline]
PHST- 2005/06/25 09:00 [entrez]
AID - 10.2174/1567205054367829 [doi]
PST - ppublish
SO  - Curr Alzheimer Res. 2005 Jul;2(3):281-90. doi: 10.2174/1567205054367829.