Mzik_2022_J.Pharm.Biomed.Anal_219_114898

Reference

Title : UHPLC-HRMS study of pharmacokinetics of a novel hybrid cholinesterase inhibitor K1234: A comparison between in silico, in vitro and in vivo data - Mzik_2022_J.Pharm.Biomed.Anal_219_114898
Author(s) : Mzik M , Sestak V , Mezeiova E , Korabecny J , Hroch M , Pejchal J , Karasova-Zdarova J
Ref : J Pharm Biomed Anal , 219 :114898 , 2022
Abstract : 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(max) within minutes, with extensive distribution into tissues and fast metabolism in mice. The dominant metabolic pathway appears to be glucuronidation of the parent molecule and its phase-I metabolites. The passage of K1234 across the blood-brain-barrier in mice appears to be limited, as it reached only approximately one third of the AUC of plasma.
ESTHER : Mzik_2022_J.Pharm.Biomed.Anal_219_114898
PubMedSearch : Mzik_2022_J.Pharm.Biomed.Anal_219_114898
PubMedID: 35779353

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Citations formats

Mzik M, Sestak V, Mezeiova E, Korabecny J, Hroch M, Pejchal J, Karasova-Zdarova J (2022)
UHPLC-HRMS study of pharmacokinetics of a novel hybrid cholinesterase inhibitor K1234: A comparison between in silico, in vitro and in vivo data
J Pharm Biomed Anal 219 :114898

Mzik M, Sestak V, Mezeiova E, Korabecny J, Hroch M, Pejchal J, Karasova-Zdarova J (2022)
J Pharm Biomed Anal 219 :114898