tacrine

b>Tacrine-E2020 hybrids and some related compounds were prepared and their bioactivities on the Alzheimer's disease were assayed. The optimum hybrid inhibitor 3 is 37-fold more potent and 31-fold more selective than tacrine in vitro.

The lipophilicity and solubility profiles of bis(12)-hupyridone (B12H) and bis(7)-tacrine (B7T), two novel acetylcholinesterase inhibitors dimerized from huperzine A fragments and tacrine, respectively, were investigated over a broad pH ..

..b>Tacrine or galanthamine, inhibitors of acetylcholinesterase, given in conjunction with scopolamine partially reversed the ..

..Antialzheimer preparations tacrine and dimebon improve survival of cerebellar granule cells during long-term incubation with Abeta25-35, the ..

Two tacrine-ferulic acid hybrids (1 A, 1 B) and three beta-carboline derivatives (BCs; 2A, 2B, 2C) were tested in vivo on 3-month-old female rats as multi-potent anti-Alzheimer drug candidates...

..b>Tacrine was the first AChEI introduced in therapy...

The present paper describes a methodology for rapid assessment of chemical and biological degradation products of tacrine and their bioactivity for acetylcholinesterase (AChE)...

..Therefore, the present study was designed to investigate the influence of antidementia drugs, tacrine and donepezil, on biochemical markers of oxidative stress, glutathione (GSH) and malondialdehyde (MDA), and ..

b>Tacrine (CAS 321-64-2) is a reversible acetylcholine esterase inhibitor that, despite exerting beneficial effects on Alzheimer's disease (AD), displays marked hepatotoxicity...

..0 +/- 3.4 microM. Comparison of hepatoprotective activities for six furocoumarins 1 - 6 suggested that oxy-substitution at the C-9 position increased the hepatoprotective activity...

Most of the side effects induced by tacrine are associated with the gastrointestinal (GI) tract...

..b>Tacrine, a cholinesterase inhibitor, has been shown to improve memory and cognitive functions in some patients with AD, ..

..In this study, post-treatment of cerebellar granule neurons with bis(7)-tacrine significantly reversed declines in mitochondrial membrane potential, ATP production, and neuronal cell death ..

Five tacrine-ferulic acid hybrids (6a-e) were designed and synthesized as multi-potent anti-Alzheimer drug candidates...

..of our study was to evaluate the effects of the apolipoprotein E (ApoE) phenotype and gender on the response to tacrine treatment in Alzheimer's disease (AD). ApoE phenotyping was performed on 76 patients treated with tacrine for AD...

b>Tacrine and PBT2 (an 8-hydroxyquinoline derivative) are well-known drugs that inhibit cholinesterases and decrease beta-amyloid (Abeta) levels by complexation of redox-active metals, respectively...

..2,2-dimethylpropionate (choline pivaloyl ester) (CPE) and the Cholinesterase inhibitors (ChEIs) Tacrine (THA) and Galantamine (GAL)...

..We determined the 2.4 A crystal structure of hCE1 in complex with tacrine, the first drug approved for treating Alzheimer's disease, and compare this structure to the Torpedo californica ..

..The novel dimers, derived from tacrine and the fragment of huperzine A (HA'), have been demonstrated to be potent and selective reversible inhibitors of ..

b>Tacrine-huperzine A hybrids (huprines) are a new class of very potent and selective acetylcholinesterase (AChE) inhibitors. Huprines were designed from tacrine and (-)-huperzine A through a conjunctive approach...

b>Tacrine is a potent and reversible inhibitor of acetylcholinesterase (AChE) in the brain. It produces tremor in animals, which is believed to be due to an increase in the brain acetylcholine level following AChE inhibition...

To examine the mechanisms underlying the anti-tremor effect of zonisamide in rats under conditions of tacrine-induced tremulous jaw movements (TJMs).

b>Tacrine, the first acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease, is associated with transaminase elevation in up to 50% of patients...

..b>Tacrine, (-)-huperzine A and (+/-)-huprine Y, the AChEI tested in the study, did not reverse the loss of neuronal ..

The purpose of the present study was to investigate the possibility of targeting an anti-Alzheimer's drug tacrine in the brain using polymeric nanoparticles...

1. The reversible cholinesterase inhibitor, tacrine (THA) was examined against the contractions of rat duodenum to acetylcholine and carbachol (cholinesterase resistant). 2...

A diverse approach to the quantitative structure-activity relationship (QSAR) of tacrine derivatives against acetylcholinesterase (AChE) activity was studied using variable selections of stepwise multiple linear regression (MLR), genetic ..

Five inhibitors of acetylcholinesterase, huperzine A, donepezil, tacrine, rivastigmine and physostigmine, were compared with regard to their effects on different molecular forms of acetylcholinesterase in cerebral cortex, hippocampus, ..

b>Tacrine belongs to the group of acetylcholinesterse (AChE) inhibitors used as drugs for treatment of Alzheimer's disease (AD)...

..the NO synthase (NOS) inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), and the NMDAR antagonist memantine, bis(7)-tacrine was found to be more potent in reducing NO-mediated excitotoxicity and the release of NO caused by glutamate...

..Thirteen patients with Alzheimer's disease (AD), 6 receiving treatment with the cholinesterase inhibitor, tacrine [tetrahydroaminoacridine (THA)], and 7 receiving no treatment, were administered 2 mg of nicotine polacrilex and ..

Glutathione conjugation of tacrine reactive metabolites depends in part on the activity of glutathione-S-transferases (GST), of which two isozymes (GST M1 and GST T1) are polymorphically expressed.

..mass spectrometry with electrospray ionization was developed and applied for the quantification of bis(7)-tacrine (B7T) in rat blood...

Bis(7)-tacrine has been shown to prevent glutamate-induced neuronal apoptosis by blocking NMDA receptors. However, the characteristics of the inhibition have not been fully elucidated...

We have recently reported that bis(7)-tacrine could prevent glutamate-induced neuronal apoptosis through NMDA receptors. In this study, we demonstrated that in cultured rat cortical neurons, bis(7)-tacrine (IC(50), 0...

The neuroprotective properties of bis(7)-tacrine, a novel dimeric acetylcholinesterase (AChE) inhibitor, on glutamate-induced excitotoxicity were investigated in primary cultured cerebellar granule neurons (CGNs)...

..The AD medication tacrine was previously shown to inhibit some forms of rodent histamine-N-methyltransferase (HNMT), but the effects of AD ..

Bis(7)-tacrine, a promising anti-Alzheimer's dimer, has been shown to have multiple neuroprotective activities in vitro. Here, we investigate whether bis(7)-tacrine attenuates focal cerebral ischemic impairment in vivo...

..After several weeks of treatment, levels of alanine aminotransferase (ALT) increase in 50% of patients treated with tacrine for Alzheimer's disease. We looked for progressive effects on DNA to explain delayed toxicity...

The current study aims to develop a specific and sensitive LC-MS/MS method for determination of bis(7)-tacrine (B7T) in rat plasma. A 100 microL plasma sample was extracted with ethyl acetate...

..The first was commercialized drug tacrine (known also as Cognex) used for treatment of cognitive manifestation of Alzheimer\'s disease (AD)...

..decade, our group has developed several series of dimeric acetylcholinesterase (AChE) inhibitors derived from tacrine and huperzine A, a unique anti-Alzheimer's drug originally discovered from a traditional Chinese medicinal plant...

Here we report that bis(7)-tacrine, a novel acetylcholinesterase inhibitor, exerts neuroprotective effects by inhibition of nitric oxide synthase...

b>Tacrine-melatonin hybrids were designed and synthesized as new multifunctional drug candidates for Alzheimer's disease...

Bis(7)-tacrine is a novel dimeric acetylcholinesterase inhibitor derived from tacrine, and has been proposed as a promising agent to treat Alzheimer's disease...

..In the current study, we investigated the effects of bis(7)-tacrine, a novel dimeric AChE inhibitor, on Abeta-induced neurotoxicity in primary cortical neurons...

..b>Tacrine is one of the three drugs approved by the FDA for the treatment of Alzheimer's disease...

..to derive a comprehensive SAR picture for the class of acetylcholinesterase (AChE) inhibitors related to tacrine, a drug currently in use for the treatment of the Alzheimer's disease...

..To investigate the relation between tacrine treatment, inheritance of ApoE epsilon4 alleles, and rate of progression, the differences in MMSE and CIBIC ..

b>Tacrine and melatonin are well-known drugs with activities as an acetylcholinesterase (AChE) inhibitor and free radical scavenger, respectively...

Acute administration of the acetylcholinesterase inhibitor tacrine to rats induces tremulous jaw movements which can be used as a valuable model of parkinsonian tremor...

..and emodin, to scavenge and/or inhibit hydroxyl radicals generated by the Fenton reaction and to protect tacrine-induced cytotoxicity in human liver derived HepG2 cells were evaluated, respectively...

b>Tacrine (THA) is an anticholinesterase drug used to manage Alzheimer's dementia, but it is not clear how its chronic use might affect response to nondepolarizing muscle relaxants...

..We have found earlier that the depolarization-induced release of acetylcholine from the brain could be inhibited by tacrine (tetrahydroaminoacridine) but the mechanism of this action of tacrine was not clarified (S. Tucek, V. Dolezal, J...

Intragastric administration (100-200 micromol/kg) of tacrine (THA) or bis(7)-THA could cause an acute and dose-dependent increase in plasma alanine aminotransferases activity in mice at 6 h after the drug administration...

..could change the levels of Abeta in plasma, we measured Abeta42 and Abeta40 plasma levels in AD subjects before tacrine treatment and at weeks 2 and 6 of treatment...

Several new 12-amino-6,7,10,11-tetrahydro-7, 11-methanocycloocta[b]quinoline derivatives (tacrine-huperzine A hybrids, huprines) have been synthesized and tested as acetylcholinesterase (AChE) inhibitors...

The effect of chronic treatment with the cholinesterase inhibitor tacrine on nicotinic receptor subtypes was investigated in human SH-SY5Y neuroblastoma cells and in a fibroblast cell line (M10 cells) stably transfected with alpha4beta2 ..

To determine the effects of cholinesterase inhibition with tacrine hydrochloride for the symptoms of Alzheimer disease in terms of cognitive performance, clinical global impression, behavior, and functional autonomy.

..In this study, the effect and mechanisms of bis(7)-tacrine (a promising anti-Alzheimer's dimer) on Abeta generation were investigated. Bis(7)-tacrine (0...

..possible effects of estrogen replacement therapy (ERT) on clinical response to the cholinesterase inhibitor tacrine in women with Alzheimer's disease (AD)...

..The American College of Physicians and American Academy of Family Physicians developed this guideline to present the available evidence on current pharmacologic treatment of dementia...

A new series of donepezil-tacrine hybrid related derivatives have been synthesised as dual acetylcholinesterase inhibitors that could bind simultaneously to the peripheral and catalytic sites of the enzyme...

A novel series of donepezil-tacrine hybrids designed to simultaneously interact with the active, peripheral and midgorge binding sites of acetylcholinesterase (AChE) have been synthesized and tested for their ability to inhibit AChE, ..

....

..The effectiveness of the 5 U.S. Food and Drug Administration-approved pharmacologic therapies for dementias in achieving clinically relevant improvements is unclear...

The present study aims to investigate the preclinical intestinal absorption of bis(7)-tacrine (B7T) using different absorption models...

..the hybrid compound lipocrine (7), whose biological profile was markedly improved relative to those of prototypes tacrine and lipoic acid...

..Methodological limitations of the existing data include small sample sizes, and the paucity of standardized psychometric measures...

..inhibitors also increased the twitches, showing a hierarchy of potencies of galantamine>physostigmine>tacrine>rivastigmine=donepezil...

In search of safer anti-Alzheimer drugs, 14 NO-donor-tacrine hybrids (1- 14) were synthesized and evaluated for their ability to inhibit cholinesterases and for vasorelaxation effects...

..The lead compound bis(7)-tacrine (2) was properly modified to confer to the new molecules the ability of chelating metals, involved in the ..

..This article attempts to focus on some of the important recent developments in understanding and management of Alzheimer disease...

..of those of selective butyrylcholinesterase inhibitors of 9-amino-1,2,3,4-tetrahydroacridine hydrochloride (tacrine) and tetraidopropylpyrophosphoramide (iso-OMPA) and a selective AChE inhibitor, donepezil, on the cholinesterase ..

Donepezil, galanthamine, and tacrine are therapeutic acetylcholinesterase (AChE) inhibitors used for the treatment of Alzheimer's disease...

..Treated patients with DLB had significantly less parenchymal Abeta deposition, which is relevant to disease management and treatment of dementia patients using ChEI...

..On the other hand, no significant effect was observed with reference memory error. Donepezil and tacrine (cholinesterase inhibitors) antagonized the muscimol-induced spatial memory deficits. Histidine (1500 mg/kg, i.p...

..If such experimental in vitro observations can be extrapolated into clinical neuroprotective properties, AChE inhibitors could positively modulate the disease course of AD...

..Their clinical utility is controversial. Many novel approaches that promise to provide more effective treatments are currently being pursued...

..results of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition by an affinity series of tacrine-hydrazinonicotinamide hybrids are described...

There are 4 centrally acting cholinesterase inhibitors (CA-ChEI) available in the US: tacrine, galantamine, rivastigmine, and donepezil. Documented clinical experience involving exposure to these agents is limited...

..We have started with the analogues of the existing drugs: tacrine, donepezil, rivastigmine and galantamine which are still of interest for many research groups...

..In this work we proposed molecular hybrids of tacrine with donepezil (fusion of these structures), in order to suggest new proposals of AChE inhibitors for future ..

..In addition, memantine and a ChEI appear to produce an additive effect resulting in a well-tolerated, effective treatment strategy...

..in the composition of CSF AChE variants were further pursued in AD patients treated with rivastigmine (n = 11) or tacrine (n = 17) in comparison to untreated AD patients (n = 5)...

..This article presents the latest information on their pharmacokinetic properties and pharmacodynamic activity. Tacrine was the first cholinesterase inhibitor approved by regulatory agencies, followed by donepezil, rivastigmine and ..

..the extracellular acetylcholine concentration in the hippocampus of rats were evaluated, and compared to that of tacrine (9-amino-1,2,3,4-tetrahydroacridine hydrochloride), a well-known and centrally acting acetylcholinesterase (AChE) ..

..Thirty-two patients suffering from dementia of several etiologies were treated with ChEIs (tacrine 19, donepezil 5, rivastigmine 8)...

..Galantamine's APL action directly addresses the nicotinic deficit in AD...

..Global clinical status of most patients was judged as improved (54%) or stable (39%) over the observation period. These findings particularly suggest that memantine in combination with AChEIs is safe and well tolerated...

AIM: To study whether tacrine and donepezil can prevent cell apoptosis induced by staurosporine in NG108-15 and Hela cell lines. METHODS: MTT assay was used to examine if staurosporine impairs cell metabolism...

..We have tacrine, donepezil, rivastigmine and galantamine...

..To evaluate effect of TAK-147 on spatial memory deficit induced by scopolamine...

..Thirty two patients were treated with ChEls for dementia (tacrine 19, donepezil 5, rivastigmine 8)...

..3 and 1.0 mg/kg significantly ameliorated ischemia-induced memory deficits dose-dependently, but tacrine had no appreciable effect...

In the search for highly selective and potent derivatives of tacrine (1a), a number of homodimeric tacrine congeners were synthesized and conducted for their effects on rat acetylcholinesterase (AChE) and human butyrylcholinesterase (..

..Differences seen between the agents in terms of efficacy in BPSD, tolerability and safety profiles may be the result of differences in neuropharmacological profiles...

..and cholinergic system regulate APP processing, current Alzheimer's therapy targets cholinergic enhancement [Tacrine, Aricept/Donezepil, Rivastigmine, Galantamine]; and regulation of inflammation by NSAIDs [Aspirin, Ibuprofen, ..

..In addition, clozapine acts to suppress the jaw movements induce by the anticholinesterase tacrine. The suppression of tacrine-induced jaw movements by clozapine occurs at a relatively low dose; clozapine ..

..In contrast, a wide array of AChEIs, including the clinically used tacrine, produce a profound increase in the firing activity of MSDB neurons, which is blocked by Atr/Scop...

..g. bethanechol) or enhance the synaptic availability of acetylcholine (e.g. tacrine, arecept)...

..increases in cholinergic tone produced by administration of a cholinesterase inhibitor tetrahydrominoacridine (tacrine) will attenuate behavioral and neurochemical deficits in cholinergic neurotransmission in the hippocampus and ..

..The results of this study will have profound public health implications by improving our understanding of the efficacy of SJW and standard antidepressants for the treatment of MinorD. ..

..This proposal aims for a better understanding of the brain mechanisms of cognitive-behavioral therapy (CBT) in order to develop novel therapies and improve the success of existing therapies. ..

..The knowledge gained from this research will enlighten future molecular approaches to treating pathologies which afflict children and adults. ..

..Three FDA- approved drugs (tacrine, donepezil and rivastigmine) for treating AD subjects belong to the category of cholinesterase (ChE) inhibitor (..

..The outcome of the proposal is to identify mechanisms by which ChEIs block potentially toxic AB levels and to utilize this property in developing novel therapeutic agents. ..

..This proposal aims for a better understanding of the state of the brain during very early abstinence from methamphetamine in order to develop novel therapies and improve the success of existing therapies. ..

..This proposal aims for a better understanding of the brain mechanisms of cognitive-behavioral therapy (CBT) in order to develop novel therapies and improve the success of existing therapies. ..

..Studying APP and BACE gene regulation is crucial to understand APP production leading to Aa generation. These studies should help developing suitable drug targets for the treatment of Alzheimer's disease. ..

..The outcome of the proposal is to identify mechanisms by which ChEIs block potentially toxic AB levels and to utilize this property in developing novel therapeutic agents. ..

..This proposal aims for a better understanding of the brain mechanisms of cognitive-behavioral therapy (CBT) in order to develop novel therapies and improve the success of existing therapies. ..

..Studying APP and BACE gene regulation is crucial to understand APP production leading to Aa generation. These studies should help developing suitable drug targets for the treatment of Alzheimer's disease. ..

..This project will examine the chemistry of parts of the brain thought to be responsible for inhibition and/or damaged by methamphetamine in methamphetamine addicts. ..

..This work will lead to a better understanding of neural circuits controlling taste and pain and how these circuits regulate analgesia in newborns. ..

..Understanding the complex interplay between the promoter domains and the transcription factors may suggest novel methods for therapeutic intervention. ..

..This career enhancement plan will enable Dr. Evans to develop expertise in patient-oriented research, and help her accomplish her goal of becoming an independent investigator. ..

..UCI, with its strong dementia research program, growing MRI capabilities and opportunity to collaborate at the nearby UCLA Brain Imaging Center, is an excellent environment for this endeavor. ..

..Hence, these projects will allow Dr Shadlen to achieve her 5-year goal of synthesis of her interests in racial differences, dementia, and epidemiology into an independent, thought-provoking research program. ..