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  • Title: TAK-147, an acetylcholinesterase inhibitor, increases choline acetyltransferase activity in cultured rat septal cholinergic neurons.
    Author: Kato K, Hayako H, Ishihara Y, Marui S, Iwane M, Miyamoto M.
    Journal: Neurosci Lett; 1999 Jan 22; 260(1):5-8. PubMed ID: 10027686.
    Abstract:
    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.
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