TAK-147, an acetylcholinesterase inhibitor, increases choline acetyltransferase activity in cultured rat septal cholinergic neurons

Neurosci Lett. 1999 Jan 22;260(1):5-8. doi: 10.1016/s0304-3940(98)00943-4.


TAK-147, a potent acetylcholinesterase (AChE) inhibitor, potentiated choline acetyltransferase (ChAT) activity in cultured rat septal cholinergic neurons in a concentration-dependent manner with an EC50 value of 4.47 nM. Donepezil, another potent AChE inhibitor, also increased ChAT activity although its potency was less than that of TAK-147. Other AChE inhibitors (rivastigmine, tacrine, physostigmine and neostigmine) showed no effect. The effects of TAK-147 were greater in the presence of NGF, suggesting a synergistic action of TAK-147 and NGF. TAK-147 and donepezil showed high affinity for sigma receptors, whereas tacrine and physostigmine did not. Haloperidol and ifenprodil, high-affinity sigma ligands, potently enhanced ChAT activity in the septal neurons. These results suggest that TAK-147 may have neurotrophic activity on central cholinergic neurons, not via AChE inhibition but possibly via an effect on tau receptors.

MeSH terms

  • Animals
  • Benzazepines / pharmacology*
  • Cells, Cultured
  • Choline O-Acetyltransferase / metabolism*
  • Cholinergic Fibers / enzymology
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Fetus / enzymology
  • Nerve Growth Factors / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Septal Nuclei / cytology
  • Septal Nuclei / drug effects*
  • Septal Nuclei / enzymology*


  • Benzazepines
  • Cholinesterase Inhibitors
  • Nerve Growth Factors
  • TAK 147
  • Choline O-Acetyltransferase