Tacrine and its derivatives in the therapy of Alzheimer’s disease

Česká verzia

Authors: Jan Korábečný ¹; Katarína Špilovská ²; Ondřej Benek ¹; Kamil Musílek ³; Ondřej Soukup ¹; Kamil Kuča ⁴
Authors place of work: Univerzita Obrany Hradec Králové, Fakulta vojenského zdravotnictví a Fakultní nemocnice Hradec Králové ¹; Univerzita Obrany Hradec Králové, Fakulta vojenského zdravotnictví ²; Univerzita Hradec Králové, Přírodovědecká fakulta a Fakultní nemocnice Hradec Králové ³; Univerzita obrany, Fakulta vojenského zdravotnictví, Centrum pokročilých studií a Fakultní nemocnice Hradec Králové ⁴
Published in the journal: Čes. slov. Farm., 2012; 61, 210-221
Category: Přehledy a odborná sdělení

Došlo 13. srpna 2012 / Přijato 19. září 2012

Summary

Cholinesterase inhibitors have beneficial effects on the cognitive, functional, and behavioural symptoms of Alzheimer’s disease (AD). Up to date, they represent almost the only drugs approved by the U.S. Food and Drug Administration agency for AD treatment. The group involves donepezil, rivastigmine and galantamine. Apart from the above mentioned cholinesterase inhibitors, memantine is used for AD treatment as well acting as N‑methyl-D-aspartate (NMDA) non-competitive antagonist. Tacrine (9-amino-1,2,3,4-tetrahydroacridine) was the first cholinesterase inhibitor approved for symptomatic AD treatment. However, its several side effects (hepatotoxicity and gastrointestinal discomfort) limited tacrine further use. Recently, novel tacrine analogues are extensively investigated in endeavour to find less toxic compounds with the “multi-target directed ligand” profile affecting more AD pathological mechanisms. The following study summarizes the knowledge of up to date published tacrine analogues, their structural aspects and biological properties. According to structural aspects, tacrine derivatives are divided into three groups, where they are discussed.

Keywords:
Alzheimer’s disease • tacrine and its derivatives • acetylcholinesterase • inhibitor

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