Disease relevance of QUINUCLIDINYL BENZILATE

• The aim of this study was to investigate differences in the distribution of muscarinic acetylcholine receptors (mAChRs) using (R,R) (123)I-iodo-quinuclidinyl-benzilate (QNB) and single photon emission computed tomography (SPECT) in dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) and age-matched controls [1].
• We analyzed the competition kinetics of quinuclidinyl benzilate (QNB) and QNB methiodide enantiomers on human NB-OK1 neuroblastoma (M1), rat cardiac (M2), and rat pancreas (M3) muscarinic binding sites [2].
• Influence of prenatal hypoxia on brain development: effects on body weight, brain weight, DNA, protein, acetylcholinesterase, 3-quinuclidinyl benzilate binding, and in vivo incorporation of [14C]lysine into subcellular fractions [3].
• Calcium influx into mouse spermatozoa activated by solubilized mouse zona pellucida, monitored with the calcium fluorescent indicator, fluo-3. Inhibition of the influx by three inhibitors of the zona pellucida induced acrosome reaction: tyrphostin A48, pertussis toxin, and 3-quinuclidinyl benzilate [4].
• Saturation binding assays with the tritiated muscarinic antagonist quinuclidinyl benzilate indicate that LMM3 cells derived from a murine mammary adenocarcinoma express a single class of functional mAchR [5].

Psychiatry related information on QUINUCLIDINYL BENZILATE

• Decreased (3H) quinuclidinyl benzilate binding to lymphocytes in Gilles de la Tourette syndrome [6].
• In this study high-affinity binding of the muscarinic cholinergic antagonist quinuclidinyl benzilate (QNB) was determined with post-mortem human brain tissue from normal young adults, age-matched ethanol abusers, and nondemented senior adults without histories of substance abuse [7].
• Deficits in iodine-labelled 3-quinuclidinyl benzilate binding in relation to cerebral blood flow in patients with Alzheimer's disease [8].
• Biphasic effects of 3-quinuclidinyl benzilate on spontaneous motor activity in mice [9].
• The patients underwent ADAS-COG psychometric assessment and SPECT brain imaging with (123)I quinuclidinyl benzilate (QNB), to demonstrate the postsynaptic muscarinic M1 receptor, before being randomised in a double blind study to receive either an acetylcholinesterase inhibitor (donepezil) or placebo for four months [10].

High impact information on QUINUCLIDINYL BENZILATE

• ACh receptor distribution was determined by iontophoretic application of ACh and mapping of ACh sensitivity and by [3H]QNB (quinuclidinyl benzilate) binding and autoradiography [3H]QNB binds with > 90% specificity to a single, saturable, high-affinity (Kd = 11.1 pM at 21 degrees C) class of binding sites [11].
• After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey [12].
• Initially, we examined the kinetics and specificity of the binding of radiolabeled quinuclidinyl benzilate ([3H]QNB) in slide-mounted, frozen tissue sections to determine that we were labeling the muscarinic cholinergic receptors as they had been described previously in biochemical pharmacological studies [13].
• Muscarinic receptors purified from porcine atria and devoid of G protein underwent a 9-27-fold decrease in their apparent affinity for the antagonists quinuclidinyl benzilate, N-methylscopolamine, and scopolamine when treated with the thiol-selective reagent N-ethylmaleimide [14].
• Binding of quinuclidinyl benzilate, a cholinergic receptor antagonist, indicated that down-regulation of external receptors was not an explanation for this effect [15].

Chemical compound and disease context of QUINUCLIDINYL BENZILATE

• We report here the ability of selected analogues of SIBA to inhibit the binding of the muscarinic antagonist quinuclidinyl benzilate (QNB) to cultured N4TG1 neuroblastoma cells and to antagonize the acetylcholine-induced contraction of guinea pig ileum [16].
• The relative proportion of super-high, high and low affinity agonist binding sites was measured in the hippocampus from individuals with dementia of the Alzheimer type (AD/SDAT), mixed (AD-MID) type and controls, using labelled quinuclidinyl benzilate ([3H]QNB) competing with unlabelled carbachol [17].
• The only differences we have found to date between SIDS and acute controls are decreases in 3H - quinuclidinyl benzilate binding to muscarinic cholinergic receptors and in 3H - kainate binding to kainate receptors in the arcuate nucleus in alternate sections of this same data set [18].
• Quinacrine altered the equilibrium binding of the muscarinic antagonist quinuclidinyl benzilate (QNB) to the muscarinic receptor in membranes from N18TG2 neuroblastoma cells [19].
• This paper reports extended structured interviews with 35 survivors, including three doctors, carried out a year later on behalf of Human Right Watch. The literature on the likeliest CW agent, 3-quinuclidinyl benzilate (BZ), and on stress as a cause of hallucinations, is reviewed [20].

Biological context of QUINUCLIDINYL BENZILATE

• By contrast, cytochalasin treatment has no effect on the numbers of mAChR as assessed by binding studies with the radioantagonist 3H-labeled quinuclidinyl benzilate, but it induces marked enhancement of carbachol-stimulated, but not basal, phosphoinositide hydrolysis [21].
• The displacement of quinuclidinyl benzilate (QNB) by carbachol yields an IC50 of 1.5 +/- 0.45 X 10(-4) M and a Hill coefficient of 0.54 +/- 0.07, indicating a heterogeneous population of binding sites [22].
• The receptor subtype nonselective muscarinic antagonists atropine (10(-4) M), scopolamine (10(-4) M), and quinuclidinyl benzilate (10(-5) M), unlike nicotinic antagonists, caused an augmentation in EPSP amplitude [23].
• Systemic injection of quinuclidinyl benzilate partially abolished low voltage fast activity (LVFA) in the neocortex of waking rats, resulting in the appearance of large irregular slow waves during Type 2 behaviors (e.g. immobility, sniffing without head movement, face washing) [24].
• We here demonstrate, by competitive binding experiments with the tritiated muscarinic antagonist quinuclidinyl benzilate that M2 subtype predominates in both tumor cell lines [25].

Anatomical context of QUINUCLIDINYL BENZILATE

• The potent muscarinic cholinergic antagonist 3-quinuclidinyl benzilate has been used to detect muscarinic acetylcholine receptors on rodent and human lymphocytes [26].
• (6) Islet-activating protein and 3-quinuclidinyl benzilate, two inhibitors of the zona pellucida-induced acrosome reaction, prevent sperm bound to ZP3-beads from undergoing the acrosome reaction [27].
• The anti-m1 antisera were shown to immunoprecipitate [3H] quinuclidinyl benzilate ([ 3H]QNB) binding activity solubilized from rat forebrain [28].
• A cell membrane fraction prepared from the mucosa exhibited specific and saturable high affinity binding of the muscarinic cholinergic antagonist [3H] quinuclidinyl benzilate (Kd = 77 +/- 9 pM) but displayed minimal specific binding of [3H]saxitoxin or [3H]yohimbine [29].
• The in vitro affinities of several psychotropic drugs for the muscarinic cholinergic binding sites of human caudate and erythrocyte were compared in competition with a tritiated antagonist (quinuclidinyl benzilate) [30].

Associations of QUINUCLIDINYL BENZILATE with other chemical compounds

• The first binding equilibrium is reached rapidly and is characterized by dissociation constants 2.7 +/- 0.4 nM and 6.7 +/- 2.5 nM in phosphate buffer (0.05 M, pH = 7.4) for 3-quinuclidinyl benzilate and N-methyl-4-piperidinyl benzilate, respectively [31].
• The effects on muscarinic receptors of these 3-alkoxy-5-methyl-6,7-dihydro-4H-thiopyrano[3,4-d]isoxazol-5 -ium (O-alkyl-S-methyl-DHTO) analogues (7a-d) were assessed in receptor-binding experiments with tritiated oxotremorine M, pirenzepine, and quinuclidinyl benzilate as ligands and were supported by studies on the isolated guinea pig ileum [32].
• Binding studies showed that McN-A-343 was 3.6-fold more potent in displacing radiolabeled quinuclidinyl benzilate from cerebral cortex muscarinic receptors (mostly M1 subtype) than from cerebellar receptors (mostly M2 subtype), whereas oxotremorine was 2.6-fold more potent in the cerebellum [33].
• After perfusing with methacholine for 2.5 hr followed by 2.5 hr in the absence of agonist, the number of quinuclidinyl benzilate binding sites returned to control levels [34].
• Brain quinuclidinyl benzilate binding sites were unaffected by nicotine treatment and did not change during the withdrawal period [35].

Gene context of QUINUCLIDINYL BENZILATE

• To study the role of central cholinergic mechanisms in hypertension, we have determined muscarinic receptors using [3H] (-)quinuclidinyl benzilate (QNB) and choline acetyltransferase (ChAT) activity in the brain regions of spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP) and renal hypertensive rats [36].
• The distribution of the muscarinic acetylcholine receptor antagonists, quinuclidinyl benzilate and quinuclidinyl benzilate methiodide (both tritiated), in rat, guinea pig, and rabbit [37].
• The AT-1 tumors completely lacked specific QNB binding [38].
• IFN-gamma also modified the muscarinic receptor by interfering with the binding of the radiolabelled antagonist quinuclidinyl benzilate [( 3H]QNB) [39].
• [3H]-methyl-quinuclidinyl benzilate (QNB) saturation experiments showed the existence of a homogeneous population of binding sites with a high affinity and low capacity (KD = 0.17 +/- 0.05 nM., Bmax = 15,000 sites per cell) [40].

Analytical, diagnostic and therapeutic context of QUINUCLIDINYL BENZILATE

• The muscarinic antagonist, quinuclidinyl benzilate (QNB), labeled with carbon 11 was used as a radioligand to visualize in vivo by positron emission tomography (PET) the central muscarinic acetylcholine receptors (mAChR) in baboons (Papio papio) [41].
• 3. Vagotomy produced a decrease in the amount of specific [3H] quinuclidinyl benzilate binding to duodenal mucosa only, suggesting that parasympathetic denervation of the small intestine does not cause mucosal hypersensitivity to acetylcholine by an increase in mAChR [42].
• MEASUREMENTS: Radioreceptor bioassay of total SAA using tritiated quinuclidinyl benzilate (QNB) binding to muscarinic receptors [43].
• The fertilization in vitro of mouse with intact zonae pellucidae by mouse cauda epididymal spermatozoa was inhibited in a concentration- dependent fashion by 3-quinuclidinyl benzilate (QNB), normally used as a specific antagonist for the muscarinic class of cholinergic receptors [44].
• Determination of 3-quinuclidinyl benzilate (QNB) and its major metabolites in urine by isotope dilution gas chromatography/mass spectrometry [45].

References