Anticipated Social and Healthcare Economic Burden of People with Alzheimer's Disease in Two Selected Regions of the Czech Republic.

Increasing life expectancy in modern society is undoubtedly due to improved healthcare, scientific advances in medicine, and the overall healthy lifestyle of the general population. However, this positive trend has led to an increase in the number of older people with a growing need for a sustainable system for the long-term care of this part of the population, which includes social and health services that are essential for a high quality of life. Longevity also brings challenges in the form of a polymorbid geriatric population that places financial pressure on healthcare systems.

Adamantane - A Lead Structure for Drugs in Clinical Practice.

The adamantane moiety is the structural backbone of numerous compounds and its discovery launched a new field of chemistry studying the approaches to the synthesis as well as the physicochemical and biological properties of organic polyhedral compounds with practical application in the pharmaceutical industry. Adamantane derivatives have proven to be very potent compounds in a wide range of applications from systemic to topical therapy. This review summarizes the currently available adamantane derivatives in clinical practice (amantadine, memantine, rimantadine, tromantadine, adapalene, saxagliptin, vildagliptin), focusing on mechanisms of action, pharmacokinetics, pharmacodynamics and clinical trials.

Outcomes of Alzheimer's disease therapy with acetylcholinesterase inhibitors and memantine.

Introduction: Alzheimer's disease (AD) is a world-wide health problem with implications for an increasing number of people and countries. Populations suffering from AD financially strain the healthcare budgets of rich and poor countries alike. Moreover, no effective treatment is available and current drugs merely slow the progression of cognitive function deterioration and overall health status toward an inevitable end point.

Intravenous application of HI-6 salts (dichloride and dimethansulphonate) in pigs: comparison with pharmacokinetics profile after intramuscular administration.

Objectives: Oxime HI-6 is an acetylcholinesterase reactivator therapeutically efficient against nerve agents. Because of their physico-chemical properties, oximes are typically applied intramuscularly (i.m.

Oximes: inhibitors of human recombinant acetylcholinesterase. A structure-activity relationship (SAR) study.

Acetylcholinesterase (AChE) reactivators were developed for the treatment of organophosphate intoxication. Standard care involves the use of anticonvulsants (e.g.

Acetylcholinesterase reactivators (HI-6, obidoxime, trimedoxime, K027, K075, K127, K203, K282): structural evaluation of human serum albumin binding and absorption kinetics.

Acetylcholinesterase (AChE) reactivators (oximes) are compounds predominantly targeting the active site of the enzyme. Toxic effects of organophosphates nerve agents (OPNAs) are primarily related to their covalent binding to AChE and butyrylcholinesterase (BChE), critical detoxification enzymes in the blood and in the central nervous system (CNS). After exposure to OPNAs, accumulation of acetylcholine (ACh) overstimulates receptors and blocks neuromuscular junction transmission resulting in CNS toxicity.

Albumin and α1-acid glycoprotein: old acquaintances.

Introduction: Albumin and α1-acid glycoprotein (AGP) are two of the most abundant proteins found in plasma. Their effect on the pharmacokinetic profile of exogenous compounds has major implications to clinical practice. Recent exploration into their possible role as diagnostic markers underlines their significance, and provides highlights their potential in medicinal applications.

Time-dependent changes of oxime K027 concentrations in different parts of rat central nervous system.

The blood-brain barrier plays a vital role in the protection of the central nervous system. It is composed of endothelial cells with tight-junctions to limit the penetration of many endogenous and exogenous compounds, particularly hydrophilic xenobiotics. Nerve agents and pesticides are groups of compounds with high penetration potential into the central nervous system.

[Intended pharmacotherapeutical approaches of Alzheimer's disease therapy].

Alzheimer's disease is a progressive neurodegenerative disorder mainly manifested by memory loss, personality changes, and cognitive dysfunction. Despite the fact that tireless research is being conducted, up-to-date pharmacotherapy of AD is presented only by two groups diverging in the mechanism of action. The larger one uses acetylcholinesterase inhibitors, and the second group is represented by the N-methyl-D-aspartate antagonist memantine.

Huperzine induces alteration in oxidative balance and antioxidants in a guinea pig model.

Objectives: Alzheimer's disease (AD) is a neurodegenerative disorder. Symptomatic treatment is available by inhibitors of acetylcholinesterase (AChE) such as rivastigmine, galantamine and donepezil. As huperzine is a promising compound for AD treatment, our study was aimed at evaluating its pertinent implications in oxidative stress.

Toxicological scoring of Alzheimer's disease drug huperzine in a guinea pig model.

Huperzine is a secondary metabolite in lycopods Huprzia and an inhibitor of acetylcholinesterase and antagonist of N-methyl-D-apartate receptor. Huperine is a suitable drug for the treatment of Alzheimer's disease as it is a part of traditional Chinese medicine. Currently, it undergoes clinical trials in the European Union and United States.

Synthesis and in vitro evaluation of 7-methoxy-N-(pent-4-enyl)-1,2,3,4-tetrahydroacridin-9-amine-new tacrine derivate with cholinergic properties.

Cholinesterase inhibitors are, so far, the only successful strategy for the symptomatic treatment of Alzheimer's disease. Tacrine (THA) is a potent acetylcholinesterase inhibitor that was used in the treatment of Alzheimer's disease for a long time. However, the clinical use of THA was hampered by its low therapeutic index, short half-life and liver toxicity.

Asoxime (HI-6) impact on dogs after one and tenfold therapeutic doses: assessment of adverse effects, distribution, and oxidative stress.

Asoxime (HI-6) is a well known oxime reactivator used for counteracting intoxication by nerve agents. It is able to reactivate acetylcholinesterase (AChE) inhibited even by sarin or soman. The present experiment was aimed to determine markers of oxidative stress represented by thiobarbituric acid reactive substances and antioxidants represented by ferric reducing antioxidant power, reduced and oxidized glutathione in a Beagle dog model.

Partition of bispyridinium oximes (trimedoxime and K074) administered in therapeutic doses into different parts of the rat brain.

The penetration of acetylcholinesterase reactivators (oximes) into the central nervous system is typically restricted by the blood-brain barrier. Although oximes are highly hydrophilic compounds, some contradictory results confirming permeation into the brain exist. The aim of this study is to verify the penetration of oximes through the blood-brain barrier and to detect their levels achieved in different brain regions 60 min after the administration.

Synthesis and in vitro evaluation of N-(Bromobut-3-en-2-yl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine as a cholinesterase inhibitor with regard to Alzheimer's disease treatment.

A new tacrine based cholinesterase inhibitor, N-(bromobut-3-en-2-yl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine (1), was designed and synthesized to interact with specific regions of human acetylcholinesterase and human butyrylcholinesterase. Its inhibitory ability towards cholinesterases was determined and compared to tacrine (THA) and 9-amino-7-methoxy-1,2,3,4-tetrahydroacridine (7-MEOTA). The assessment of IC50 values revealed 1 as a weak inhibitor of both tested enzymes.

Synthesis and in vitro evaluation of N-alkyl-7-methoxytacrine hydrochlorides as potential cholinesterase inhibitors in Alzheimer disease.

All approved drugs for Alzheimer disease (AD) in clinical practice ameliorate the symptoms of the disease. Among them, acetylcholinesterase inhibitors (AChEIs) are used to increase the cholinergic activity. Among new AChEI, tacrine compounds were found to be more toxic compared to 7-MEOTA (9-amino-7-methoxy-1,2,3,4-tetrahydroacridine).

Passive diffusion of acetylcholinesterase oxime reactivators through the blood-brain barrier: influence of molecular structure.

In this in vitro study, high-performance liquid chromatography (HPLC) was used to determinate the penetration of 30 acetylcholinesterase (AChE) reactivators through the blood-brain barrier (BBB). According to our method, monoquaternary AChE reactivators were found to be able to penetrate the BBB. In addition to molecular structure, molecular weight appears to be an important factor for passive transport of oximes through the BBB.