Abstract
The anticholinesterase effects of bls(7)-tacrine were compared with tacrine in vitro and in vivo. Based on IC50ratios, the dimeric analog bis(7)-tacrine was, in a reversible manner, up to 150-fold more potent and 250-fold more selective than tacrine for acetylcholinesterase (ACHE) over butyrylcholinesterase (BChE). Following a single oral administration, both bis(7)-tacrine and tacrine produced close-dependent inhibitions of AChE in rat brain, but bis(7)-tacrine exhibited higher efficacy and AChE/BChE selectivity than tacrine. The anti-AChE efficacy of bis(7)-tacrine was quite similar following an oral or i.p. administration, but tacrine showed much lower efficacy when administered orally than when given i.p. These findings suggest bis(7)-tacrine, a highly potent and selective inhibitor of ACHE, can probably be used as an improved drug in the palliative treatment of AD.
| Original language | English |
|---|---|
| Pages (from-to) | 789-793 |
| Number of pages | 5 |
| Journal | NeuroReport |
| Volume | 10 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 17 Mar 1999 |
| Externally published | Yes |
Keywords
- Acetylcholinesterase
- Alzheimer's disease
- Bis(7)-tacrine
- Cholinesterase inhibitor
- Tacrine
ASJC Scopus subject areas
- General Neuroscience