UHPLC-HRMS study of pharmacokinetics of a novel hybrid cholinesterase inhibitor K1234: A comparison between in silico, in vitro and in vivo data

Autor:	M. Mzik, V. Sestak, E. Mezeiova, J. Korabecny, M. Hroch, J. Pejchal, J. Karasova-Zdarova
Rok vydání:	2022
Předmět:	Mice Alzheimer Disease Clinical Biochemistry Drug Discovery Acetylcholinesterase Pharmaceutical Science Acridines Animals Cholinesterase Inhibitors Spectroscopy Chromatography High Pressure Liquid Analytical Chemistry
Zdroj:	Journal of pharmaceutical and biomedical analysis. 219
ISSN:	1873-264X
Popis:	Alzheimer's disease (AD) is one of the most common forms of dementia. Current anti-AD therapeutics exploit the cholinergic hypothesis of its pathophysiology; they aim to inhibit cerebral cholinesterases. K1234 is a novel hybrid molecule derived from Huperzine A and 7-MEOTA-huperzine which shows increased potency in acetylcholinesterase inhibition in vitro compared to the compounds themselves. The study focused on description of the pharmacokinetic behaviour of K1234, blood-brain barrier penetration, identification of the main in vitro and in vivo metabolites. K1234 is relatively non-toxic compound, that is rapidly absorbed after i.p. administration reaching C
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7784a1f31116c6b7548ff398dc21eea3 https://pubmed.ncbi.nlm.nih.gov/35779353 Zobrazit plný text záznamu Full Text from ScienceDirect