ФЕНСЕРИН

Использование

Phenserine is inhibitor of amyloid precursor protein (APP). Used in Alzheimer’s treatments.

Биологическая активность

Physostigmine analog that inhibits acetylcholinesterase. Inhibits production of amyloid precursor protein (APP) and A β . Improves morris water maze performance of scopolamine-treated rats.

Ферментативный ингибитор

This long-acting AChE inhibitor and A?42-lowering agent (FW = 337,42 g/mol; CAS 101246-66-6), also known as (–) -N-phenylcarbamoyl eseroline, is a carbamate analogue of eserine (or physostigmine) that inhibits acetylcholinesterase and is under active investigation for its potential in cholinomimetic therapy to reduce cognitive impairments associated with aging and Alzheimer's Disease. Phenserine is a potent and highly selective AChE inhibitor (IC50 = 22 nM), displaying 70x greater inhibitory action than observed with butyrylcholinesterase, or BChE (IC50 = 1560 nM), both in vitro and in clinical trials for treatment of Alzheimer's disease (1-5). Compared to physostigmine and tacrine, phenserine appears to be less toxic and robustly enhances cognition in animal models. In rats, phenserine achieves maximum acetylcholinesterase inhibition of 73.5% at 5 min, maintaining high and relatively constant inhibition for >8 hours. Phenserine decreased the levels of secreted b-amyloid precursor protein (b- APP) in the cerebrospinal fluid (CSF) of forebrain cholinergic system- lesioned rats, whereas DFP, a relatively non-specific cholinesterase inhibitor, failed to affect CSF levels of secreted b-APP. Such findings suggest that phenserine alters the induction of cortical b-APP mRNAs and increased levels of secreted b-APP in the CSF. Phenserine reduces Ab levels by regulating b-APP translation via a recently described iron regulatory element in the 5'-untranslated region of b-APP mRNA that was previously shown to be up-regulated in the presence of interleukin-1. Other dual AChE/A?42 inhibitors include: rivastigmine, ladostigil, asenapine, phenserine, amitriptyline, clomipramine, doxepin and desipramine. Posiphen, the better-tolerated (+) -enantiomer of phenserine, is devoid of anticholinesterase action, but represses translation of neural α- synuclein, a druggable target in the treatment of Parkinson Disease.