PMID- 23238976
OWN - NLM
STAT- MEDLINE
DCOM- 20140110
LR  - 20211021
IS  - 1435-1463 (Electronic)
IS  - 0300-9564 (Linking)
VI  - 120
IP  - 6
DP  - 2013 Jun
TI  - Propargylamine-derived multitarget-directed ligands: fighting Alzheimer's disease 
      with monoamine oxidase inhibitors.
PG  - 893-902
LID - 10.1007/s00702-012-0948-y [doi]
AB  - Alzheimer's disease (AD) is a complex neurodegenerative disorder with a 
      multifaceted pathogenesis. There are at present three Food and Drug 
      Administration-approved drugs based on the "one drug, one target" paradigm 
      (donepezil, galantamine and rivastigmine) that improve symptoms by inhibiting 
      acetylcholinesterase. However, apart from the beneficial palliative properties, 
      cholinergic drugs have shown little efficacy to prevent the progression of the 
      disease evidencing the unsuitability of this strategy for the complex nature of 
      AD. By contrast, the multifactorial nature of this neurodegenerative disorder 
      supports the most current innovative therapeutic approach based on the "one drug, 
      multiple targets" paradigm, which suggests the use of compounds with multiple 
      activities at different target sites. Accordingly, the also called 
      multitarget-directed ligand (MTDL) approach has been the subject of increasing 
      attention by many research groups, which have developed a variety of hybrid 
      compounds acting on very diverse targets. The therapeutic potential of monoamine 
      oxidase inhibitors (MAOI) in AD has been suggested due to their demonstrated 
      neuroprotective properties besides their enhancing effect on monoaminergic 
      transmission. Especially, those containing a propargylamine moiety are of 
      particular interest due to their reported beneficial actions. Therefore, 
      targeting MAO enzymes should be considered in therapeutic interventions. This 
      review makes a special emphasis on MTDLs that commonly target MAO enzymes. There 
      is at present an urgent need for real disease-modifying therapies for AD and the 
      MTDL approach makes a breakthrough for the development of new drugs capable of 
      addressing the biological complexity of this disorder.
FAU - Bolea, Irene
AU  - Bolea I
AD  - Departament of Biochemistry and Molecular Biology, Faculty of Medicine, 
      Neuroscience Institute, Universitat Autonoma de Barcelona, Bellaterra, 08193, 
      Barcelona, Spain.
FAU - Gella, Alejandro
AU  - Gella A
FAU - Unzeta, Mercedes
AU  - Unzeta M
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20121213
PL  - Austria
TA  - J Neural Transm (Vienna)
JT  - Journal of neural transmission (Vienna, Austria : 1996)
JID - 9702341
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Ligands)
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 0 (Propylamines)
RN  - 2450-71-7 (propargylamine)
RN  - 9MV14S8G3E (Pargyline)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
SB  - IM
MH  - Acetylcholinesterase
MH  - Alzheimer Disease/*drug therapy
MH  - Animals
MH  - Cholinesterase Inhibitors/chemistry/pharmacology/therapeutic use
MH  - Humans
MH  - Ligands
MH  - Monoamine Oxidase Inhibitors/chemistry/*therapeutic use
MH  - Pargyline/*analogs & derivatives/chemistry/pharmacology/therapeutic use
MH  - Propylamines/chemistry/*pharmacology/*therapeutic use
EDAT- 2012/12/15 06:00
MHDA- 2014/01/11 06:00
CRDT- 2012/12/15 06:00
PHST- 2012/10/14 00:00 [received]
PHST- 2012/12/02 00:00 [accepted]
PHST- 2012/12/15 06:00 [entrez]
PHST- 2012/12/15 06:00 [pubmed]
PHST- 2014/01/11 06:00 [medline]
AID - 10.1007/s00702-012-0948-y [doi]
PST - ppublish
SO  - J Neural Transm (Vienna). 2013 Jun;120(6):893-902. doi: 
      10.1007/s00702-012-0948-y. Epub 2012 Dec 13.