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MeSH: inhibitory katechol-O-methyltransferasy

31 záznamů v Medvik Filtry

Článek

Moderní farmakoterapie Parkinsonovy nemoci
[Modern pharmacotherapy of Parkinson's disease]

Menšíková, Kateřina
Autor Autorita ORCID Neurologická klinika LF UP a FN Olomouc

Klinická farmakologie a farmacie. 2024 ; 38 (2) : 60-66. [pub] 20240715

ISSN 1212-7973
Medvik
Zdroj

Léčba Parkinsonovy nemoci je v současnosti stále léčbou symptomatickou a její management je primárně zaměřen na kontrolu motorických projevů. Hlavním pilířem současné terapie zůstávají dopaminergní preparáty nahrazující působení chybějícího dopaminu. Významného pokroku bylo v posledních desetiletích dosaženo v možnostech terapie pokročilého stadia onemocnění pomocí intervenčních metod, jako je léčba pumpovými systémy a hluboká mozková stimulace. Důležitou součástí léčby je ovlivnění non-motorických symptomů, které významně ovlivňují kvalitu života pacientů. Nové léčebné strategie schopné ovlivnit rozvoj a progresi onemocnění, které jsou stále ve fázi preklinického a klinického výzkumu, zahrnují nejrůznější léčebné postupy s cílem ovlivnit tvorbu a agregaci patologických forem alfa-synukleinu a modifikovat šíření patologického procesu v mozku.

Despite intensive research, the current treatment of Parkinson's disease is still symptomatic treatment and its management is primarily aimed at controlling motor symptoms. Dopaminergic agents that replace the action of the missing dopamine remain the mainstay of current therapy. In recent decades, significant progress has been made in the treatment of advanced stage of disease using interventional methods such as treatment with pump systems and deep brain stimulation. An important part of the treatment is the influence of non-motor symptoms, which significantly affect the quality of life of patients. New treatment strategies capable to affect the development and progression of the disease, which are still in the preclinical and clinical research phase, include various treatment procedures with the aim to influence the formation and aggregation of pathological forms of alpha-synuclein and modify the spread of the pathological process in the brain.

Článek

Pharmacophore-based virtual screening of catechol-o-methyltransferase (COMT) inhibitors to combat Alzheimer's disease

Journal of biomolecular structure & dynamics. 2018 ; 36 (15) : 3938-3957. [pub] 20171227

J Biomol Struct Dyn
ISSN 1538-0254
Medvik
Zdroj

Alzheimer's disease (AD) is one of the most significant neurodegenerative disorders and its symptoms mostly appear in aged people. Catechol-o-methyltransferase (COMT) is one of the known target enzymes responsible for AD. With the use of 23 known inhibitors of COMT, a query has been generated and validated by screening against the database of 1500 decoys to obtain the GH score and enrichment value. The crucial features of the known inhibitors were evaluated by the online ZINC Pharmer to identify new leads from a ZINC database. Five hundred hits were retrieved from ZINC Pharmer and by ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering by using FAF-Drug-3 and 36 molecules were considered for molecular docking. From the COMT inhibitors, opicapone, fenoldopam, and quercetin were selected, while ZINC63625100_413 ZINC39411941_412, ZINC63234426_254, ZINC63637968_451, and ZINC64019452_303 were chosen for the molecular dynamics simulation analysis having high binding affinity and structural recognition. This study identified the potential COMT inhibitors through pharmacophore-based inhibitor screening leading to a more complete understanding of molecular-level interactions.