New classes of AChE inhibitors with additional pharmacological effects of interest for the treatment of Alzheimer's disease.

Article Details

Citation

Copy to clipboard

Villarroya M, Garcia AG, Marco JL

New classes of AChE inhibitors with additional pharmacological effects of interest for the treatment of Alzheimer's disease.

Curr Pharm Des. 2004;10(25):3177-84.

PubMed ID

15544507 [ View in PubMed

]

Abstract

Alzheimer's disease (AD) is associated to a gradual loss of attention and memory that have been associated to impairment of brain cholinergic neurotransmission, particularly a deficit of cholinergic neurons in the nucleus basalis of Meynert. Thus, it is not surprising that the first therapeutic target that has demonstrated therapeutic efficacy on cognition, behaviour and functional daily activities has been the inhibitors of acetylcholinesterase (AChE), i.e. tacrine, donepezil, rivastigmine and galanthamine. But not all inhibitors of AChE have the same potency to block the enzyme and have a different pharmacological profile. For instance, rivastigmine is a dual inhibitor of AChE and butyrylcholinesterase (BuChE), and galanthamine is a mild inhibitor of AChE and an allosteric potentiating ligand of neuronal nicotinic receptors for acetylcholine (nAChRs). In addition, we have recently found that galanthamine has neuroprotective effects by inducing calcium signals and the induction of the antiapoptotic protein Bcl-2. In this frame, we have been synthesizing new tacrine derivatives that keep their ability to inhibit AChE but that interfere with neuronal calcium overloading and prevent apoptosis. Some of these compounds exhibit neuroprotecting properties and thus, could be useful in the treatment of neurodegenerative and ischaemic brain diseases.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tacrine	Acetylcholinesterase	Protein	Humans	Yes	Inhibitor	Details