1-Benzyl-4-methylpiperidinyl moiety in donepezil: The priority ticket across the blood-brain-barrier in rats

Karasová, Jana Žďárová; Šesták, Vít; Korábečný, Jan; Mezeiová, Eva; Palička, Vladimír; Kuča, Kamil; Mzik, Martin

doi:10.1016/j.jchromb.2018.06.034

Cited by 4 publications

(1 citation statement)

References 26 publications

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“…Other in vivo pharmacokinetic studies have highlighted the capacity of donepezil and its fragments to cross the BBB by passive diffusion, as previously confirmed by other researchers who reported that the concentrations of donepezil in the brain expressed as the area-under-the-curve of the concentration, exceed plasma concentrations in mice, rats, and rabbits [90,91]. A series of studies showed that high doses of donepezil (23 mg) were more effective than lower doses (5 and 10 mg) and that pharmacological effects depended not only on dose increase and drug formulation, but also on the mechanism of active efflux along the blood-brain barrier, P-glycoprotein being a determining factor in the efflux of donepezil from the central compartment to the bloodstream [92,93].…”

Section: Synthetic Analoguesmentioning

confidence: 99%

Alzheimer’s Disease Pharmacotherapy in Relation to Cholinergic System Involvement

et al. 2019

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Alzheimer’s disease, a major and increasing global health challenge, is an irreversible, progressive form of dementia, associated with an ongoing decline of brain functioning. The etiology of this disease is not completely understood, and no safe and effective anti-Alzheimer’s disease drug to prevent, stop, or reverse its evolution is currently available. Current pharmacotherapy concentrated on drugs that aimed to improve the cerebral acetylcholine levels by facilitating cholinergic neurotransmission through inhibiting cholinesterase. These compounds, recognized as cholinesterase inhibitors, offer a viable target across key sign domains of Alzheimer’s disease, but have a modest influence on improving the progression of this condition. In this paper, we sought to highlight the current understanding of the cholinergic system involvement in Alzheimer’s disease progression in relation to the recent status of the available cholinesterase inhibitors as effective therapeutics.

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Section: Synthetic Analoguesmentioning

confidence: 99%

Alzheimer’s Disease Pharmacotherapy in Relation to Cholinergic System Involvement

et al. 2019

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Tacrine and its 7-methoxy derivate; time-change concentration in plasma and brain tissue and basic toxicological profile in rats

Karasová

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Korábečný

et al. 2019

Drug and Chemical Toxicology

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The pharmacokinetic parameters and the effect of a single and repeated doses of memantine on gastric myoelectric activity in experimental pigs

et al. 2020

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Background Memantine, currently available for the treatment of Alzheimer's disease, is an uncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors. Under normal physiologic conditions, these unstimulated receptor ion channels are blocked by magnesium ions, which are displaced after agonist-induced depolarization. In humans, memantine administration is associated with different gastrointestinal dysmotility side effects (vomiting, diarrhoea, constipation, motor-mediated abdominal pain), thus limiting its clinical use. Mechanism of these motility disorders has not been clarified yet. Pigs can be used in various preclinical experiments due to their relatively very similar gastrointestinal functions compared to humans. The aim of this study was to evaluate the impact of a single and repeated doses of memantine on porcine gastric myoelectric activity evaluated by means of electrogastrography (EGG). Methods Six adult female experimental pigs (Sus scrofa f. domestica, mean weight 41.7±5.0 kg) entered the study for two times. The first EGG was recorded after a single intragastric dose of memantine (20 mg). In the second part, EGG was accomplished after 7-day intragastric administration (20 mg per day). All EGG recordings were performed under general anaesthesia. Basal (15 minutes) and study recordings (120 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Running spectral analysis based on Fourier transform was used. Results were expressed as dominant frequency of gastric slow waves (DF) and power analysis (areas of amplitudes).

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1-Benzyl-4-methylpiperidinyl moiety in donepezil: The priority ticket across the blood-brain-barrier in rats

Cited by 4 publications

References 26 publications

Alzheimer’s Disease Pharmacotherapy in Relation to Cholinergic System Involvement

Alzheimer’s Disease Pharmacotherapy in Relation to Cholinergic System Involvement

Tacrine and its 7-methoxy derivate; time-change concentration in plasma and brain tissue and basic toxicological profile in rats

The pharmacokinetic parameters and the effect of a single and repeated doses of memantine on gastric myoelectric activity in experimental pigs

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