A novel muscarinic receptor ligand which penetrates the blood brain barrier and displays in vivo selectivity for the m2 subtype.

Abstract:

:Alzheimer's disease (AD) involves selective loss of muscarinic m2, but not m1, subtype neuroreceptors in the posterior parietal cortex of the human brain. Emission tomographic study of the loss of m2 receptors in AD is limited by the fact that there is currently no available m2-selective radioligand which can penetrate the blood-brain barrier. In our efforts to prepare such a radioligand, we have used competition studies against currently existing muscarinic receptor radioligands to infer the in vitro and in vivo properties of a novel muscarinic receptor ligand, 5-[[4-[4-(diisobutylamino)butyl]-1-phenyl]acetyl]-10,11-dihydro-5H - -dibenzo [b,e][1,4]diazepin-11-one (DIBD). In vitro competition studies against [3H](R)-3-quinuclidinylbenzilate ([3H]QNB) and [3H]N-methylscopolamine ([3H]NMS), using membranes derived from transfected cells expressing only m1, m2, m3, or m4 receptor subtypes, indicate that DIBD is selective for m2/m4 over m1/m3. In vivo competition studies against (R,R)-[125I]IQNB indicate that DIBD crosses the blood brain barrier (BBB). The relationship of the regional percentage decrease in (R,R)-[125I]IQNB versus the percentage of each of the receptor subtypes indicates that DIBD competes more effectively in those brain regions which are known to be enriched in the m2, relative to the m1, m3, and m4, receptor subtype; however, analysis of the data using a mathematical model shows that caution is required when interpreting the in vivo results. We conclude that a suitably radiolabeled derivative of DIBD may be of potential use in emission tomographic study of changes in m2 receptors in the central nervous system.

journal_name

Life Sci

journal_title

Life sciences

authors

Gitler MS,Cohen VI,De la Cruz R,Boulay SF,Jin B,Zeeberg BR,Reba RC

doi

10.1016/0024-3205(93)90161-u

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

1743-51

issue

23

eissn

0024-3205

issn

1879-0631

pii

0024-3205(93)90161-U

journal_volume

53

pub_type

杂志文章
  • Stimulation of muscarinic cholinoceptive neurons in the hippocampus evokes a pressor response with bradycardia.

    abstract::The injection of neostigmine into the hippocampus of anesthetized rats increased the mean arterial blood pressure (17% of baseline after 60 min injection) and decreased the heart rate (24% of baseline after 60 min injection). These changes were blocked by the co-administration of methylatropine into the hippocampus. I...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(92)90377-2

    authors: Haruta K,Iguchi A,Matsubara T,Itoh K,Chen CL,Yoshida S,Terada R,Kanashiro M,Suzuki O,Nishimura H

    更新日期:1992-01-01 00:00:00

  • MiR-27b suppresses epithelial-mesenchymal transition and chemoresistance in lung cancer by targeting Snail1.

    abstract:HEADING AIMS:MicroRNA-27b (miR-27b) has been shown to play a role in the progression of many different forms of cancer, but its specific relevance in the context of non-small cell lung cancer (NSCLC) remains uncertain. As such, this study sought to explore the role of miR-27b in NSCLC and the mechanisms whereby it func...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2019.117238

    authors: Zhang J,Hua X,Qi N,Han G,Yu J,Yu Y,Wei X,Li H,Chen X,Leng C,Liu Q,Lu Y,Li Y

    更新日期:2020-08-01 00:00:00

  • Diurnal variations of S-adenosyl-L-methionine and adenosine content in the rat pineal gland.

    abstract::S-adenosylmethionine and adenosine levels in the rat pineal gland were determined by high-performance liquid chromatography after fractionation of the pineal extracts. The concentration of S-adenosylmethionine follows a circadian rhythm and is about three times higher during the day (2.5 nmol/gland) than the night (1....

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(84)90253-4

    authors: Chabannes B,Sarda N,Cronenberger L,Pacheco H

    更新日期:1984-08-06 00:00:00

  • GABA as a trophic factor during development.

    abstract::The process of synaptogenesis has been studied by many investigators to determine the factors which regulate synapse formation. We have used neonatal rabbit retina to investigate the role of the gamma-aminobutyric acid (GABA) neurotransmitter system during development. By utilizing an in vitro incubation treatment of ...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(83)90754-3

    authors: Madtes P Jr,Redburn DA

    更新日期:1983-09-05 00:00:00

  • Regional differences of the mouse brain in response to an α-linolenic acid-restricted diet: Neurotrophin content and protein kinase activity.

    abstract:AIMS:The purpose of this study was to determine a relatively short-term effect of feeding an α-linolenic acid (ALA, n-3)-restricted, linoleic acid (LA, n-6)-adequate diet on neurotrophin contents and protein kinase activities in brain regions of the mouse. MAIN METHODS:After feeding mice a safflower oil (SAF) diet (AL...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2010.09.003

    authors: Miyazawa D,Yasui Y,Yamada K,Ohara N,Okuyama H

    更新日期:2010-10-09 00:00:00

  • Carbonic anhydrase inhibition, antioxidant activity against alveolar epithelial cells and antibacterial effect against Klebsiella pneumoniae enabled by synthesized silica nanoparticles through laser ablation technique.

    abstract::Silica (SiO2) nanoparticles (NPs) were synthesized by laser ablation method and were characterized by TEM and DLS techniques. Afterwards, their inhibition activity against carbonic anhydrase (CA) isoforms (CA I and CA II) was explored by experimental and theoretical analysis. Also, the protective effect of SiO2 NPs ag...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2021.119032

    authors: Xu N,Lu W,Meng L,Feng X,Xuan J,Liu F,Feng Z

    更新日期:2021-01-12 00:00:00

  • Effects of dopamine metabolites on locomotor activities and on the binding of dopamine: relevance to the side effects of L-dopa.

    abstract::L-dopa is the major treatment for Parkinson's disease (PD), but its efficacy is limited by the presence of dyskinesia. The dyskinesia develops over a period of exposure to L-dopa and is related to the dosage, therefore, the cause may involve inductive changes that produce toxic levels of metabolites, interfering with ...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(00)00543-9

    authors: Charlton CG,Crowell B Jr

    更新日期:2000-04-21 00:00:00

  • Differential inhibition by alpha and epsilonPKC pseudosubstrate sequences: a putative mechanism for preferential PKC activation in neonatal cardiac myocytes.

    abstract::The aims of the current study were: 1) to determine if the epsilonPKC pseudosubstrate peptide (epsilonphi) (NH(2)-RKRQGAVRRRVHQVNG-COOH) could be used as an epsilonPKC-selective inhibitor in neonatal cardiac myocytes (NCMs) and 2) to determine if differences in the alpha and epsilonPKC autoinhibitory pseudosubstrate m...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2003.11.016

    authors: Johnson JA

    更新日期:2004-05-07 00:00:00

  • Azelnidipine treatment reduces the expression of Cav1.2 protein.

    abstract:AIMS:Azelnidipine, a third-generation dihydropyridine calcium channel blocker (DHP CCB), has a characteristic hypotensive effect that persists even after it has disappeared from the plasma, which is thought to be due to its high hydrophobicity. However, because azelnidipine is unique, it might have other unknown effect...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2021.119043

    authors: Nasu F,Obara Y,Okamoto Y,Yamaguchi H,Kurakami K,Norota I,Ishii K

    更新日期:2021-01-13 00:00:00

  • Leukotriene D4 role in allergic asthma pathogenesis from cellular and therapeutic perspectives.

    abstract::Asthma is a chronic inflammatory and allergic disease that is mainly characterized by reversible airway obstruction and bronchial hyperresponsiveness. The incidence of asthma is increasing with more than 350 million people worldwide are affected. Up to now, there is no therapeutic option for asthma and most of the pre...

    journal_title:Life sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.lfs.2020.118452

    authors: Al-Azzam N,Elsalem L

    更新日期:2020-11-01 00:00:00

  • Phosphoesterase complex modulates microflora and chronic inflammation in rats with alcoholic fatty liver disease.

    abstract::Phosphoesterase complex (Pho), a major active component of barley malt, has been demonstrated to be clinically effective in relieving alcoholic fatty liver disease (AFLD), and several lines of evidence have suggested that microbial dysbiosis, caused by chronic alcohol overconsumption, plays a key role in the progressi...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2020.118509

    authors: Ma D,Hu J,Xu W,Wang Y,Wang J,Li L,Wang S,Zhou H,Li Y,Liu L

    更新日期:2020-12-01 00:00:00

  • The effects of flavonoids on human phenolsulphotransferases: potential in drug metabolism and chemoprevention.

    abstract::Flavonoids are frequently found in fruits and vegetables, and are currently under investigation as potential chemopreventive agents. The present study reports the inhibitory effects of six flavonoids, quercetin, genistein, daidzein, equol, (+)-catechin and flavone, on sulphation of p-nitrophenol, a model substrate for...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(99)00423-3

    authors: Ghazali RA,Waring RH

    更新日期:1999-01-01 00:00:00

  • Proconflict effect of carbon dioxide inhalation in rats.

    abstract::The effect of brief inhalation of carbon dioxide (CO2) was studied in a conflict situation (Vogel test) in the rat. This treatment, which inhibits gamma-aminobutyric acid (GABA)-mediated transmission in rat brain and induces anxiety and panic attacks in humans, elicited a proconflict effect. Exposure of rats for 1 min...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(95)00093-3

    authors: Cuccheddu T,Floris S,Serra M,Porceddu ML,Sanna E,Biggio G

    更新日期:1995-03-10 00:00:00

  • Inhibition of adenylate cyclase activity by polyamines in human erythrocyte plasma membranes.

    abstract::Polyamines (spermidine, spermine and putrescine) inhibited the adenylate cyclase activity in a concentration dependent manner in human erythrocyte plasma membranes. Spermidine (Spd) exhibited more inhibitory effect than spermine (Spm) and putrescine (Put). On the contrary, the addition of amino acids (arginine, glutam...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(90)90055-v

    authors: Khan NA,Quemener V,Moulinoux P

    更新日期:1990-01-01 00:00:00

  • The influence of reproductive hormones on ANF release by rat atria.

    abstract::The effects of subcutaneous (sc) administration of estradiol (50 micrograms/100 microliters/day x 10 day) or testosterone (15 mg/100 microliters twice a week x 2 weeks) on ANF release were examined in isolated perfused rat atria. The concentration of ANF in the perfusate was measured by radioimmunoassay, under basal c...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(93)90245-x

    authors: Deng Y,Kaufman S

    更新日期:1993-01-01 00:00:00

  • Inhibition of avian and mammalian hydroxy-indole-o-methyl-transferase (HIOMT) with low molecular weight fractions of mammalian pineal glands.

    abstract::Partially purified fractions from sheep pineal gland extracts, which show a fluorescence like pteridines, were shown to suppress the enzyme hydroxy-indole-o-methyltransferase (HIOMT) isolated from avian pineals and retinas. The results described demonstrate that the mechanism of inhibition of HIOMT activity is indepen...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(82)90022-4

    authors: Ebels I,Cremer-Bartels G

    更新日期:1982-04-19 00:00:00

  • Melanin concentrating hormone. III. Melanin concentrating hormone (MCH): the message sequence.

    abstract::Melanin concentrating hormone (MCH) is a heptadecapeptide synthesized by the hypothalamus and secreted by the neurohypophysis of the teleost pituitary gland. MCH stimulates melanosome aggregation within teleost melanocytes but also exhibits MSH-like (melanosome dispersing) activity on tetrapod (frog and lizard) melano...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(89)90501-8

    authors: Castrucci AM,Lebl M,Hruby VJ,Matsunaga TO,Hadley ME

    更新日期:1989-01-01 00:00:00

  • Hepatic mitochondrial enzyme activity and serum amino acid composition in rats treated with tumor necrosis factor.

    abstract::The biochemical integrity of hepatocellular mitochondria was investigated in rats treated with small doses of human recombinant tumor necrosis factor-alpha (Hur-TNF;50-100 micrograms/kg/d injected intraperitoneally for 5 d) by measuring the activities of three mitochondrial enzymes, glutamate dehydrogenase, succinate ...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(94)00495-e

    authors: Yasmineh WG,Tsai MY,Theologides A

    更新日期:1995-01-01 00:00:00

  • Molecular docking prediction and in vitro studies elucidate anti-cancer activity of phytoestrogens.

    abstract:AIM:The study is aimed at evaluating the chemosensitization and apoptotic effect of aglycone rich extracts of dietary phytoestrogens (derived from soybean and flaxseed) on estrogen receptor positive, MCF-7 and estrogen receptor negative, MDA-MB-231 cells. The extracts show potent activity on both the cell lines, hence,...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2017.07.015

    authors: Dutta S,Kharkar PS,Sahu NU,Khanna A

    更新日期:2017-09-15 00:00:00

  • Inhibition of extracellular ATP degradation in endothelial cells.

    abstract::The plasma membrane ATPase on the human umbilical vein endothelial cell line (ECV304) was demonstrated to be an ecto-enzyme. Hydrolysis of ATP was measured by monitoring the appearance of inorganic phosphorus. Hydrolysis of extracellular ATP was insensitive to oligomycin, vanadate, ouabain and N-ethylmaleimide, compou...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(95)02004-3

    authors: Meghji P,Burnstock G

    更新日期:1995-01-01 00:00:00

  • Enzyme linked immunosorbent assay (ELISA) for beta-endorphin and its antibodies.

    abstract::A sensitive method for quantitation of beta-endorphin in biological fluids and tissues using ELISA methodology has been developed. This assay is sensitive to as low as 30 picograms of beta-endorphin per measurement and can be carried out in approximately 5 hours. The determination of antibody titer levels to beta-endo...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(83)90461-7

    authors: Sarma JM,Houghten RA

    更新日期:1983-01-01 00:00:00

  • Influences of maternal caffeine on the neonatal rat brains vary with the nutritional states.

    abstract::The potential effect of maternal caffeine ingestion upon total brain protein and the concentration of two prototype neuropeptides, thyrotropin-releasing hormone (TRH) and its derivative, cyclo (His-Pro) in neonates was examined during the nursing period in the context of variable maternal protein intake. Maternal caff...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(83)90332-6

    authors: Mori M,Wilber JF,Nakamoto T

    更新日期:1983-11-21 00:00:00

  • Aerobic exercise attenuates ectopic renal sinus adipose tissue accumulation-related renal hypoxia injury in obese mice.

    abstract:AIMS:We explored the effect of aerobic exercise on renal sinus adipose (RSA) accumulation and RSA accumulation-related renal injury in obese mice. MAIN METHODS:C57BL/6J male mice (n = 30) were evenly divided into three groups: control group (CON, n = 10), obese group (OB, n = 10; given high-fat diet) and obese + aerob...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2021.119106

    authors: Wang SS,Gu Q,Liu N,Li J,Liu X

    更新日期:2021-01-23 00:00:00

  • Characterization of human, dog and rabbit corpus cavernosum type 5 phosphodiesterases.

    abstract::Human, dog and rabbit corpus cavernosum type 5 phosphodiesterases (PDE5) were isolated and their characteristics were compared. The three enzymes showed Km values of 0.8, 2.1 and 2.3 uM, respectively. They exhibited similar pH-dependence with optimal pH being 7.5. They required Mg++ for activity and the activity was s...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(01)00989-4

    authors: Wang P,Wu P,Myers JG,Stamford A,Egan RW,Billah MM

    更新日期:2001-03-16 00:00:00

  • Overexpression of long non-coding RNA SNHG16 against cerebral ischemia-reperfusion injury through miR-106b-5p/LIMK1 axis.

    abstract::Long non-coding RNA (LncRNA) involved in types of physiological insults and diseases via regulating the responses of complex molecular, including cerebral ischemia-reperfusion (I/R) injury. LncRNA SNHG16 played a potential role in ketamine-induced neurotoxicity. In this study, we utilized an in vitro cell model of I/R...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2020.117778

    authors: Pan H,Zhao F,Yang Y,Chang N

    更新日期:2020-08-01 00:00:00

  • LncRNA HOX transcript antisense RNA accelerated kidney injury induced by urine-derived sepsis through the miR-22/high mobility group box 1 pathway.

    abstract:OBJECTIVE:This study investigated the role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in kidney injury induced by urine-derived sepsis (US). MATERIALS AND METHODS:An Escherichia coli suspension was injected into the distal ureter of adult male Sprague Dawley rats to establish a US model. Lipo...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2018.08.041

    authors: Shen J,Zhang J,Jiang X,Wang H,Pan G

    更新日期:2018-10-01 00:00:00

  • Nitric oxide signaling participates in norepinephrine-induced activity of neuronal intracellular survival pathways.

    abstract::Much evidence has gathered that nitric oxide (NO) signaling, via cGMP-dependent mechanisms, may activate pro-survival pathways in hippocampal neurons and inhibit apoptosis. Past research has revealed that the enhancement of monoaminergic neurotransmission via exercise or treatment with antidepressant medications leads...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2007.09.003

    authors: Chen MJ,Russo-Neustadt AA

    更新日期:2007-09-29 00:00:00

  • Effects of dietary caffeine on renal handling of minerals in adult women.

    abstract::Thirty-seven women, aged 31-78 years, on two separate mornings consumed a decaffeinated beverage to which 6 mg caffeine/kg lean body mass or no caffeine were added. Total urine output of water, calcium, magnesium, sodium, chloride, potassium and creatinine increased in the two hours following caffeine ingestion when c...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(90)90616-y

    authors: Bergman EA,Massey LK,Wise KJ,Sherrard DJ

    更新日期:1990-01-01 00:00:00

  • Surgical and pharmacological reductions in sympathetic nerve activity increase the neuropeptide Y-immunoreactivity content of the rat iris but not the vas deferens.

    abstract::Decentralization of the superior cervical ganglion (S.C.G.) of the rat elevated the neuropeptide-Y immunoreactivity (NPY-ir) content of the ganglion on day 1 (+43%) but not on day 3 post-surgery. The content of NPY-ir in the iris was increased by decentralization (+40%) 3 days post-surgery, and treatment with clonidin...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(88)90333-5

    authors: Maccarrone C,Jarrott B

    更新日期:1988-01-01 00:00:00

  • Flow dependent changes in the effective surface area of microdialysis probes.

    abstract::The relative efficiencies of microdialysis probes were determined both in vitro and in vivo using tritiated water. Tritiated water (THO) freely distributes throughout the fluid spaces of an experimental animal and, at equilibrium, the brain extracellular concentration of THO is the same as the plasma concentration. Mi...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(88)90063-x

    authors: Alexander GM,Grothusen JR,Schwartzman RJ

    更新日期:1988-01-01 00:00:00