At present, Alzheimer's disease (AD) and related dementias cannot be cured. Therefore, scientists all over the world are trying to find a new approach to prolong an active life of patients with initial dementia. Both pharmacological and non-pharmacological pathways are investigated to improve the key symptom of the disease, memory loss. In this respect, influencing the neuromodulator acetylcholine via muscarinic receptors, such as cevimeline, might be one of the therapeutic alternatives. The purpose of this study is to explore the potential of cevimeline on the cognitive functions of AD patients. The methodology is based on a systematic literature review of available studies found in Web of Science, PubMed, Springer, and Scopus on the research topic. The findings indicate that cevimeline has shown an improvement in experimentally induced cognitive deficits in animal models. Furthermore, it has demonstrated to positively influence tau pathology and reduce the levels of amyloid-β (Aβ) peptide in the cerebral spinal fluid of Alzheimer's patients. Although this drug has not been approved by the FDA for its use among AD patients and there is a lack of clinical studies confirming and extending this finding, cevimeline might represent a breakthrough in the treatment of AD.

• Klíčová slova
• AF102B, Alzheimer disease, SNI2011, cevimeline, cholinergic agonist, cognition, evoxac, memory, muscarinic receptors, neurodegeneration,
• MeSH
• agonisté muskarinových receptorů farmakologie   MeSH
• chinuklidiny farmakologie   MeSH
• kognitivní poruchy farmakoterapie   MeSH
• léčivé přípravky aplikace a dávkování   MeSH
• lidé MeSH
• neurodegenerativní nemoci farmakoterapie   MeSH
• neurofarmakologie * MeSH
• thiofeny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• agonisté muskarinových receptorů MeSH
• cevimeline MeSH Prohlížeč
• chinuklidiny MeSH
• léčivé přípravky MeSH
• thiofeny MeSH

10-Methylacridinium iodide (methylacridinium; MA) is an inhibitor of cholinesterases. Inhibitors of acetylcholinesterase (AChE) are used in the treatment of myasthenia gravis, Alzheimer's disease, and in the prophylaxis of poisoning with organophosphates. Using spectrophotometric Ellman's method at 436 nm and commercial enzymes we found that MA inhibits AChE by binding with relatively high potency to the peripheral anionic site (IC(50) = 1.68 +/- 0.14 1M; human recombinant AChE) and equally to its inhibition of butyrylcholinesterase (BuChE; IC(50) = 3.54 +/- 0.27 1M; BuChE from human serum). MA also inhibits the binding of [(3)H]N-methylscopolamine to the muscarinic M2 receptor subtype, possibly in an allosteric manner (IC(50) = 1.90 1M). Functional effects on both the enzyme and the receptor could be observed in contractile studies on the isolated rat bladder. The ability of MA to cross the blood-brain barrier (log P = -0.32; polar surface area 3.88) provides prerequisites for a potential use of the drug in the treatment of neural disorders.

• MeSH
• acetylcholinesterasa chemie   farmakologie   MeSH
• akridiny chemie   MeSH
• butyrylcholinesterasa krev   chemie   farmakologie   MeSH
• chemické modely * MeSH
• cholinergní látky farmakologie   MeSH
• hematoencefalická bariéra účinky léků   fyziologie   MeSH
• inhibiční koncentrace 50 MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• močový měchýř účinky léků   metabolismus   MeSH
• myši MeSH
• počítačová simulace MeSH
• potkani Sprague-Dawley MeSH
• prasata MeSH
• regresní analýza MeSH
• sérum metabolismus   MeSH
• srdce účinky léků   MeSH
• substrátová specifita MeSH
• vazba proteinů účinky léků   MeSH
• vazebná místa účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• akridiny MeSH
• butyrylcholinesterasa MeSH
• cholinergní látky MeSH
• N-methylacridine MeSH Prohlížeč