Abstract:
:An important aspect of brain cholinesterase function is related to enzymatic differences. The brain of mammals contains two major forms of cholinesterases: acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The two forms differ genetically, structurally and for their kinetics. Butyrylcholine is not a physiological substrate in mammalian brain which makes the function of BuChE of difficult interpretation. In human brain, BuChE is found in neurons and glial cells as well as in neuritic plaques and tangles in Alzheimer disease (AD) patients. While AChE activity decreases progressively in the brain of AD patients, BuChE activity shows some increase. In order to study the function of BuChE, we perfused intracortically the rat brain with a selective BuChE inhibitor and found that extracellular acetylcholine increased 15 fold from 5 to 75nM concentrations with little cholinergic side effects in the animal. Based on these data and on clinical data showing a relation between CSF BuChE inhibition and cognitive function in AD patients, we postulated that two pools of cholinesterases may be present in brain, the first mainly neuronal and AChE dependent and the second mainly glial and BuChE dependent. The two pools show different kinetic properties with regard to regulation of ACh concentration in brain and can be separated with selective inhibitors. Within particular conditions, such as in mice nullizygote for AChE or in AD patients at advanced stages of the disease, BuChE may replace AChE in hydrolyzing brain acetylcholine. Based on the changes of ChE activity in the brain of AD patients, a rational indication of selective BuChEI (or of mixed double function inhibitors) is the treatment of advanced cases. A second novel aspect of ChEI therapy is the emerging of new indications which include various forms of dementia such as dementia with Lewy Bodies, Down Syndrome, vascular dementia and Parkinson Dementia. Clinical results demonstrate examples of versatility of cholinergic enhancement.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Giacobini Edoi
10.1016/j.phrs.2003.11.017keywords:
subject
Has Abstractpub_date
2004-10-01 00:00:00pages
433-40issue
4eissn
1043-6618issn
1096-1186pii
S1043661804000854journal_volume
50pub_type
杂志文章,评审abstract::There is considerable evidence to support the role of anandamide (AEA), an endogenous ligand of cannabinoid receptors, in neuropathic pain modulation. AEA also produces effects mediated by other biological targets, of which the transient receptor potential vanilloid type 1 (TRPV1) has been the most investigated. Both,...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.06.012
更新日期:2016-09-01 00:00:00
abstract::The effects of the angiotensin-converting enzyme (ACE) inhibitor monopril and the angiotensin II receptor blocker losartan on serum glucose, protein levels and some serum lipid components were compared in normal and diabetic rats receiving oral antidiabetic drugs 'repaglinide or gliclazide'. The two antihypertensive a...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2003.12.019
更新日期:2004-08-01 00:00:00
abstract::Diabetes is a chronic metabolic disease characterized by hyperglycemia and several associated biochemical abnormalities. Diabetes leads to multiorgan complications that collectively reduce life expectancy. Hematopoietic stem cells (HSCs) are nested within bone marrow (BM) niches whence they can be mobilized to the per...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2018.07.017
更新日期:2018-09-01 00:00:00
abstract::Exaggerated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling is key to the pathogenesis of pro-inflammatory disorders, such as rheumatoid arthritis and cardiovascular diseases. Mutational activation of JAKs is also responsible for several haematological malignancies, including myelop...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2017.10.001
更新日期:2018-02-01 00:00:00
abstract::We have studied the effect of acute trazodone (3--20 mg kg(-1)) and quipazine (1--3 mg kg(-1)) treatment on the apomorphine-induced (1 mg kg(-1), once daily over 2 weeks) aggressive behaviour in male Wistar rats. All doses of trazodone and quipazine tested attenuated the aggressiveness as evidenced by the abolished in...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2000.0790
更新日期:2001-04-01 00:00:00
abstract::Male weanling Wistar rats were fed a 4% cholestyramine diet and used as a model to demonstrate that a reduction in serum low density lipoproteins stimulates de novo cholesterogenesis leading to DNA synthesis and cell proliferation. Feeding this diet resulted in a decrease in serum very low density lipoproteins and low...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/1043-6618(89)90195-3
更新日期:1989-09-01 00:00:00
abstract::Isoxanthohumol (IXN), a prenylated flavonoid from hops, exhibits diverse biological activities, e.g. antitumor, antiinflammatory, antioxidant and antiangiogenic. In this study, the effect of IXN is evaluated on two melanoma cell lines with dissimilar molecular background, B16 and A375. The treatment of both cell lines...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.01.011
更新日期:2016-03-01 00:00:00
abstract::Treatment of pediatric diabetes can be challenging. Strict glucose control can be accompanied by hypoglycemia and weight gain. Recently, there have been many developments in insulin preparations and delivery methods which make insulin levels more close to a physiologic pattern. Newly developed rapid/long acting analog...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2011.08.011
更新日期:2012-01-01 00:00:00
abstract::Recent studies clearly show that there is a relationship between endotoxemia and impaired vascular responsiveness. The aim of this study was to investigate whether treatment with the new potent PARP inhibitor PJ34 could prevent the vascular hyporesponsiveness induced by lipopolysaccharide (LPS). Endotoxemia was induce...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2005.02.020
更新日期:2005-06-01 00:00:00
abstract::Epidemiological studies support an inverse correlation between HDL-C and cardiovascular disease. However, low HDL-C levels do not always segregate with premature disease. These include, LCAT deficiency and the apolipoproteinA-IMilano (AIM) variant. AIM has a cysteine for arginine at position 173 in the otherwise cyste...
journal_title:Pharmacological research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.phrs.2016.05.001
更新日期:2016-09-01 00:00:00
abstract::MicroRNAs (miRNAs) are small non-coding RNAs that regulate post-transcriptional gene expression by targeting specific mRNAs for degradation or translation repression. Changes in miRNAs expression profiles have been reported in several neurodegenerative disorders such as Alzheimer's disease (AD) and related tauopathies...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2020.104729
更新日期:2020-05-01 00:00:00
abstract::This study was performed in order to investigate the cholinomimetic response of seminal vesicles isolated from rats treated with hydrocortisone acetate during perinatal life. At the adult phase, the body weight and the wet weight of the seminal vesicle of these animals were unchanged. However, these male rats exhibite...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::Atropine (5 mg/kg, s.c., twice daily) had no significant effect on 24-h water consumption on day 1 of treatment; on subsequent days the rats showed a significant increase. Procyclidine (5 mg/kg, s.c., twice daily) had a similar effect, except that the increase in daily water consumption began on the third day of treat...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/1043-6618(90)90745-y
更新日期:1990-01-01 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) is a debilitating condition where excess collagen deposition occurs in the extracellular matrix. At first sight, it is expected that the level of different kinds of matrix metalloproteinases might be downregulated in IPF as it is a matrix degrading collagenase. However, the role of ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.104591
更新日期:2020-02-01 00:00:00
abstract::A bovine dopamine transporter (bDAT) cDNA was transfected into CV-1 cells, a cell line that lacks vesicular storage and release mechanisms. Using this cell line, the effects of neuroleptic drugs on DAT-mediated uptake and release of dopamine (DA) were examined. All of the neuroleptic drugs tested, inhibited DA uptakes...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:
更新日期:1997-05-01 00:00:00
abstract::The smoothened (SMO) receptor, an essential signal transducer in the Hedgehog pathway, was targeted with antagonists to suppress the tumor. It is interesting that SMO D473H mutation confers resistance on inhibitor LDE-225 rather than LEQ-506. In this paper, the binding modes of them against the wild type and mutant SM...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2017.11.025
更新日期:2018-03-01 00:00:00
abstract::Carbon-based nanomaterials have unique physicochemical properties relevant to the diagnosis and treatment of various diseases. There have been many reports indicating that carbon nanomaterials (CNMs) can interact and perturb biomolecules such as proteins and amyloid structures. This review is an attempt to reflect the...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.03.023
更新日期:2019-05-01 00:00:00
abstract::Protein tyrosine phosphatases (PTPs), which are ubiquitously expressed in hematopoietic and non-hematopoietic cells, are critical for regulating cell proliferation as well as differentiation in the physiology of multicellular organisms. PTPs regulate the intracellular signaling mechanism of immune cells via dephosphor...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.04.011
更新日期:2019-06-01 00:00:00
abstract::Recent studies have shown that a higher consumption of green tea leads to a lower prevalence of depressive symptoms in elderly individuals. However, no studies have explored the antidepressant-like effect of green tea in preclinical models of depression. The aim of this study was to investigate the antidepressant-like...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2011.09.007
更新日期:2012-01-01 00:00:00
abstract::Advanced glycation end-products (AGE) and the receptor for AGE (RAGE) have been linked to numerous diabetic vascular complications. RAGE activation promotes a self-sustaining state of chronic inflammation and has been shown to induce apoptosis in various cell types. Although previous studies in vascular smooth muscle ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2015.12.015
更新日期:2016-02-01 00:00:00
abstract::Breast cancer (BC) is the most common cancer in women, and the second most frequent cause of cancer-related deaths in women worldwide. It is a heterogeneous disease composed of multiple subtypes with distinct morphologies and clinical implications. Quantitative systems pharmacology (QSP) is an emerging discipline brid...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2017.07.015
更新日期:2017-10-01 00:00:00
abstract::There is evidence that hydrazine, a metabolite of isoniazid, plays an important role in the mechanism of isoniazid-induced hepatotoxicity. Hydrazine has been reported to be metabolised by NADPH cytochrome P-450 reductase (reductase) to reactive and potentially toxic intermediates. The present study was designed, using...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1998.0347
更新日期:1998-09-01 00:00:00
abstract::Osteopontin (OPN) is known as an active player in the progression of vascular remodeling diseases, however, the precise role in the proliferation of vascular smooth muscle cells (VSMC) is unclear. Thus, this study investigated the role of OPN in VSMC proliferation induced by 4-hydroxynonenal (HNE), and identified the ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.03.041
更新日期:2016-06-01 00:00:00
abstract::As one classic anticancer drug, clinical application of Doxorubicin (Dox) is limited due to its side effects. In our previous work, we have investigated the drug targets to treat Dox-induced cardiotoxicity, hepatotoxicity and nephrotoxicity. In this paper, the mechanisms and new drug-target associated with Dox-induced...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2019.104276
更新日期:2019-08-01 00:00:00
abstract::Effect of moclobemide, a selective monoamine oxidase-type A enzyme inhibitor, was investigated on the body temperature of male mice. Moclobemide (15-30 mg kg(-1), i.p.) produced significant reductions of body temperature in both normal and yeast-induced hyperthermic male mice. The hypothermic effect of moclobemide was...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043-6618(03)00108-7
更新日期:2003-09-01 00:00:00
abstract::Availability of highly active antiretroviral therapy has dramatically increased survival rates and substantially modified the course of HIV infection, which has now become a chronic disease both in adults and in children. Treatment strategies in paediatric patients have to face with specific challenges associated with...
journal_title:Pharmacological research
pub_type: 社论,评审
doi:10.1016/j.phrs.2011.01.007
更新日期:2011-07-01 00:00:00
abstract::Cicletanine [(+/-)-C] is a racemic furopyridine derivative used as an antihypertensive agent. Pharmacokinetic and metabolic studies have shown that cicletanine is rapidly and almost fully metabolized into sulfo- and glucuro-conjugated metabolites. However, the stereoselective metabolism of cicletanine is not well-know...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2000.0660
更新日期:2000-07-01 00:00:00
abstract::The aim of this study was to investigate effect of antiemetics on G6PD and antioxidant enzymes. Antiemetics are currently being used to reduce or prevent nausea and vomiting in patients. This is the first study to show effect of antiemetics on glucose-6-phosphate dehydrogenase (G6PD) and antioxidant enzyme activities....
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2004.05.007
更新日期:2004-11-01 00:00:00
abstract::Antioxidants have a great potential as adjuvant therapeutics in patients with Duchenne muscular dystrophy, although systematic comparisons at pre-clinical level are limited. The present study is a head-to-head assessment, in the exercised mdx mouse model of DMD, of natural compounds, resveratrol and apocynin, and of t...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.02.016
更新日期:2016-04-01 00:00:00
abstract::Disruption of the circadian clock is associated with a variety of human pathologies, including cancer. Rather than being a mere consequence of a global changes associated with the cancer cell transcriptome, the aberrant clock gene expression observed in many tumors may serve for cancer cell survival. This scenario sug...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2015.08.008
更新日期:2015-10-01 00:00:00