Centrally acting anticholinesterases

Anticholinesterases Centrally acting + CYP3A4 inducers and inhibitors... 

Cholinomimetics that can increase central cholinergic activity have produced some improvements in Alzheimer s disease AChE inhibitors, particularly physostigmine, have been most studied. A study with an experimental potent, centrally acting anticholinesterase compound l,2,3,4-tetrahydro-9-aminoacridine (THA, Tacrine) involving Alzheimer s patients over a year-long period showed encouraging improvement without some side effects. 

The effects of centrally-acting anticholinesterases (e.g. donepeziQ are expected to be additive with those of other anticholinesterases (e.g. neost mine) and cholinergics (e.g. pilocarpine). The effects of centrally-acting anticholinesterases and drugs with antimus-carinic effects are expected to be antagonistic. 

The interaetions that affect the antimuscarinic effects of these drugs are discussed in this section. However, the antimuscarinics also affect the actions of other drugs (such as the centrally-acting anticholinesterases) and these are therefore discussed elsewhere in the publication. 

Parkinsonism is due to an imbalance between two neurotransmitters, dopamine and acetylcholine, in the basal ganglia of the brain. Centrally acting anticholinesterases increase the amount of acetylcholine in the brain, which could lead to an exacerbation of parkinsonian symptoms. Levodopa improves the situation by increasing the levels of dopamine. It is not known why donepezil modestly increased the levels of levodopa. 

Also in the CNS, increased ACh levels give rise to overactivity of central neurons causing spike discharges and fitting. This is sign of serious anticholinesterase poisoning and acts with peripheral NM paralysis to worsen the developing h3T)oxia. 

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