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3 Quinuclidinyl Benzilate Poisoning

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3-Quinuclidinyl-α-methoxydiphenylacetate: A multi-targeted ligand with antimuscarinic and antinicotinic effects designed for the treatment of anticholinesterase poisoning.

Christopher M Timperley, Mike Bird, Samuel J Gore, Christopher D Lindsay, Helen Rice, John E H Tattersall, Charlotte L Whitmore, A Christopher Green,

Racemic 3-quinuclidinyl-α-methoxydiphenylacetate (MB266) was synthesised. Its activity at muscarinic acetylcholine receptors (mAChRs), and muscle and neuronal nicotinic acetylcholine receptors (nAChRs), was compared to that of atropine and racemic 3-quinucidinyl benzilate (QNB) using a functional assay based on agonist-induced elevation of intracellular calcium ion concentration in CN21, Chinese Hamster Ovary (CHO) ... Read more >>

Toxicol. Lett. (Toxicology letters)
[2020, 325:67-76]

Cited: 0 times

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M1 muscarinic receptor is a key target of neuroprotection, neuroregeneration and memory recovery by i-Extract from Withania somnifera.

Arpita Konar, Richa Gupta, Rajendra K Shukla, Bryan Maloney, Vinay K Khanna, Renu Wadhwa, Debomoy K Lahiri, Mahendra K Thakur,

Memory loss is one of the most tragic symptoms of Alzheimer's disease. Our laboratory has recently demonstrated that 'i-Extract' of Ashwagandha (Withania somnifera) restores memory loss in scopolamine (SC)-induced mice. The prime target of i-Extract is obscure. We hypothesize that i-Extract may primarily target muscarinic subtype acetylcholine receptors that regulate ... Read more >>

Sci Rep (Scientific reports)
[2019, 9(1):13990]

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Drugs Interfering with Muscarinic Acetylcholine Receptors and Their Effects on Place Navigation.

Jan Svoboda, Anna Popelikova, Ales Stuchlik,

Muscarinic acetylcholine receptors (mAChRs) have been found to regulate many diverse functions, ranging from motivation and feeding to spatial navigation, an important and widely studied type of cognitive behavior. Systemic administration of non-selective antagonists of mAChRs, such as scopolamine or atropine, have been found to have adverse effects on a ... Read more >>

Front Psychiatry (Frontiers in psychiatry)
[2017, 8:215]

Cited: 4 times

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Neuroimmune Communication in Health and Disease.

Colin Reardon, Kaitlin Murray, Alan E Lomax,

The immune and nervous systems are tightly integrated, with each system capable of influencing the other to respond to infectious or inflammatory perturbations of homeostasis. Recent studies demonstrating the ability of neural stimulation to significantly reduce the severity of immunopathology and consequently reduce mortality have led to a resurgence in ... Read more >>

Physiol. Rev. (Physiological reviews)
[2018, 98(4):2287-2316]

Cited: 4 times

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A 7-methoxytacrine-4-pyridinealdoxime hybrid as a novel prophylactic agent with reactivation properties in organophosphate intoxication.

E Nepovimova, J Korabecny, R Dolezal, T D Nguyen, D Jun, O Soukup, M Pasdiorova, P Jost, L Muckova, D Malinak, L Gorecki, K Musilek, Kamil Kuca,

Chemical warfare agents constitute an increasing threat to both military and civilian populations. Therefore, effective prophylactic approaches are urgently needed. Herein, we present a novel hybrid compound which is able not only to keep acetylcholinesterase resistant to organophosphate (OP) inhibitors, but also to serve as an enzyme reactivator in the ... Read more >>

Toxicol Res (Camb) (Toxicology research)
[2016, 5(4):1012-1016]

Cited: 4 times

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Possible role for anisodamine in organophosphate poisoning.

Arik Eisenkraft, Avshalom Falk,

In cases of organophosphate poisoning, patients are treated with a combination of antidotes. In addition to these poison-directed antidotes, patients may require extra oxygen and artificial ventilation; other modalities may also be needed due to the wide range of toxic effects. Anisodamine is a belladonna alkaloid, and like other drugs ... Read more >>

Br. J. Pharmacol. (British journal of pharmacology)
[2016, 173(11):1719-1727]

Cited: 4 times

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Downregulation of nicotinic and muscarinic receptor function in rats after subchronic exposure to diazinon.

Saša R Ivanović, Blagoje Dimitrijević, Vitomir Ćupić, Milanka Jezdimirović, Sunčica Borozan, Mila Savić, Djordje Savić,

Diazinon (DZN) is an organophosphate insecticide which exerts its effect through the inhibition of acetylcholinesterase enzyme (AChE). In this work, we studied the development of tolerance to subchronic p.o. administration of DZN in rats, under both in vivo and in vitro conditions. A group of 20 rats (2 groups, n = 10) ... Read more >>

Toxicol Rep (Toxicology reports)
[2016, 3:523-530]

Cited: 3 times

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"Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies".

Tanara V Peres, Maria Rosa C Schettinger, Pan Chen, Fabiano Carvalho, Daiana S Avila, Aaron B Bowman, Michael Aschner,

Manganese (Mn) is an essential heavy metal. However, Mn's nutritional aspects are paralleled by its role as a neurotoxicant upon excessive exposure. In this review, we covered recent advances in identifying mechanisms of Mn uptake and its molecular actions in the brain as well as promising neuroprotective strategies. The authors ... Read more >>

BMC Pharmacol Toxicol (BMC pharmacology & toxicology)
[2016, 17(1):57]

Cited: 40 times

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Toxin-Induced Experimental Models of Learning and Memory Impairment.

Sandeep Vasant More, Hemant Kumar, Duk-Yeon Cho, Yo-Sep Yun, Dong-Kug Choi,

Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated ... Read more >>

Int J Mol Sci (International journal of molecular sciences)
[2016, 17(9):]

Cited: 10 times

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The effect of oxime reactivators on muscarinic receptors: functional and binding examinations.

O Soukup, U K Kumar, J Proska, L Bratova, A Adem, D Jun, J Fusek, K Kuca, G Tobin,

The antidotal treatment of organophosphorus poisoning is still a problematic issue since no versatile antidote has been developed yet. In our study, we focused on an interesting property, which does not relate to the reactivation of inhibited acetylcholinesterase (AChE) of some oximes, but refers to their anti-muscarinic effects which may ... Read more >>

Environ. Toxicol. Pharmacol. (Environmental toxicology and pharmacology)
[2011, 31(3):364-370]

Cited: 8 times

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Targeting cholinesterase inhibitor poisoning with a novel blocker against both nicotinic and muscarinic receptors.

Wangqian Luo, Xulin Ge, Wenyu Cui, Hai Wang,

Clinicians have been treating poisoning by acetylcholinesterase inhibitors (ChEI) for more than half a century. However, the current atropine-centered therapy still cannot protect completely against all ChEIs, and poisoning by ChEIs is fatal in more than 20% of cases. Various solutions that try to enhance atropine's antimuscarinic effects have been ... Read more >>

Neurotox Res (Neurotoxicity research)
[2010, 18(2):173-186]

Cited: 1 time

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The 2012 core content of medical toxicology.

Lewis S Nelson, Beth A Baker, Kevin C Osterhoudt, Curtis P Snook, , Julia N Keehbauch, ,

J Med Toxicol (Journal of medical toxicology : official journal of the American College of Medical Toxicology)
[2012, 8(2):183-191]

Cited: 5 times

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M1 and M3 muscarinic receptors may play a role in the neurotoxicity of anhydroecgonine methyl ester, a cocaine pyrolysis product.

Raphael Caio Tamborelli Garcia, Livia Mendonça Munhoz Dati, Larissa Helena Torres, Mariana Aguilera Alencar da Silva, Mariana Sayuri Berto Udo, Fernando Maurício Francis Abdalla, José Luiz da Costa, Renata Gorjão, Solange Castro Afeche, Mauricio Yonamine, Colleen M Niswender, P Jeffrey Conn, Rosana Camarini, Maria Regina Lopes Sandoval, Tania Marcourakis,

The smoke of crack cocaine contains cocaine and its pyrolysis product, anhydroecgonine methyl ester (AEME). AEME possesses greater neurotoxic potential than cocaine and an additive effect when they are combined. Since atropine prevented AEME-induced neurotoxicity, it has been suggested that its toxic effects may involve the muscarinic cholinergic receptors (mAChRs). ... Read more >>

Sci Rep (Scientific reports)
[2015, 5:17555]

Cited: 5 times

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[The influence of aminostigmine on the parameters of nonspecific resistance and immune system of the organism upon acute poisoning of benzyl 3-quinuclidylate]

Zabrodskiĭ, Troshkin, Germanchuk, Sidel'nikova, Lim,

The results of experiments on outbred rats weighing 180 -240 g showed that the acute poisoning with benzyl 3-quinuclidylate decreases the parameters of nonspecific resistance of the organism, reduces the antibody production mainly to T-dependent antigens (sheep red blood cells), decreases the activity of natural killers and the antibody-dependent cell-mediated ... Read more >>

Eksp Klin Farmakol (Eksperimental'naia i klinicheskaia farmakologiia)
[2005, 68(6):40-42]

Cited: 0 times

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Lymphocyte cytochrome c oxidase, cyclic GMP and cholinergic muscarinic receptors as peripheral indicators of carbon monoxide neurotoxicity after acute and repeated exposure in the rat.

Anna F Castoldi, Teresa Coccini, Giovanna Randine, Mariluz Hernández-Viadel, Vicente Felipo, Luigi Manzo,

Changes in cerebral cytochrome oxidase (COX) activity, nitric oxide (NO)-cyclic GMP (cGMP) pathway and cholinergic muscarinic receptors (MRs) have been reported in rodents acutely exposed to carbon monoxide (CO). These endpoints measurable in lymphocytes may serve as peripheral markers of CO neurotoxicity. The early and delayed effects of repeated and ... Read more >>

Life Sci. (Life sciences)
[2006, 78(17):1915-1924]

Cited: 3 times

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Neurochemical and electrophysiological diagnosis of reversible neurotoxicity in earthworms exposed to sublethal concentrations of CL-20.

Ping Gong, Niladri Basu, Anton M Scheuhammer, Edward J Perkins,

BACKGROUND, AIM, AND SCOPE: Hexanitrohexaazaisowurtzitane (CL-20) is a relatively new energetic compound sharing some degree of structural similarity with hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a known neurotoxic compound. Previously, we demonstrated using a noninvasive electrophysiological technique that CL-20 was a more potent neurotoxicant than RDX to the earthworm Eisenia fetida. In the present ... Read more >>

Environ Sci Pollut Res Int (Environmental science and pollution research international)
[2010, 17(1):181-186]

Cited: 3 times

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Cholinergic denervation-like changes in rat hippocampus following developmental lead exposure.

H Bielarczyk, X Tian, J B Suszkiw,

We investigated the effects of developmental lead exposure from embryonic day 16 (E16) through postnatal day 28 (PN28), on cholinergic and catecholaminergic markers in the septohippocampal pathway in rats through fourth month of age. Lead exposure resulted in a persistent 30-40% reduction of [3H]hemicholinium-3 ([3H]HC-3) binding in the hippocampus through ... Read more >>

Brain Res. (Brain research)
[1996, 708(1-2):108-115]

Cited: 18 times

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Low-level exposure to methylmercury modifies muscarinic cholinergic receptor binding characteristics in rat brain and lymphocytes: physiologic implications and new opportunities in biologic monitoring.

T Coccini, G Randine, S M Candura, R E Nappi, L D Prockop, L Manzo,

Methylmercury (MeHg) affects several parameters of cholinergic function. These alterations are thought to play a role in MeHg neurotoxicity. In vitro experiments have indicated that MeHg acts as a strong competitive inhibitor of radioligand binding to muscarinic cholinergic receptors (mAChRs) in rat brain. Furthermore, rat brain mAChRs share several pharmacologic ... Read more >>

Environ. Health Perspect. (Environmental health perspectives)
[2000, 108(1):29-33]

Cited: 50 times

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Complementary improvement of the method for determining cholinergic activities in the small intestine and its application to experiments in vivo.

H Kobayashi, I Sato, S Fujii, Y Akatsu, T Suzuki, N Matsusaka, A Yuyama,

The concentration of acetylcholine (ACh) in rat jejunum that had been homogenized with an ultra-high-speed homogenizer (Biotron) was significantly higher than that in jejunum homogenized with a glass homogenizer. Rats were injected once or repeatedly for 10 days with a muscarinic agonist, pilocarpine (1 mg/kg), or a muscarinic antagonist, scopolamine ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[1994, 19(3):133-140]

Cited: 0 times

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Human erythrocyte as a model for investigating muscarinic agonists and antagonists.

L C Tang,

1. Human erythrocyte muscarinic receptor is further classified as M1 subtype by its binding of [3H]pirenzepine (a specific M1 antagonist). Conversely, binding of [3H]piperidinyl AF-DX116 (a specific M2 antagonist) is not detected. 2. There are high correlations between the binding efficacies of 25 known or putative cholinergic agents using either ... Read more >>

Gen. Pharmacol. (General pharmacology)
[1991, 22(3):485-490]

Cited: 3 times

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Trihexyphenidyl enhances physostigmine prophylaxis against soman poisoning in guinea pigs.

D K Lim, B Hoskins, I K Ho,

The protective effects of simultaneous and continuous administration of physostigmine and trihexyphenidyl against soman-induced toxicity were studied in guinea pigs. Not only did trihexyphenidyl reduce physostigmine-induced toxicity when it was administered continuously to the animals along with physostigmine, the combination afforded greater protection from soman lethality than did either agent ... Read more >>

Fundam Appl Toxicol (Fundamental and applied toxicology : official journal of the Society of Toxicology)
[1991, 16(3):482-489]

Cited: 9 times

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[Modification of selective adsorption of muscarinic antagonists in cerebral membranes during chlorophos poisoning]

Predtechenskiĭ, Elaeva, Smirnova,

Using radioligand assay it was demonstrated that chlorophos intoxication produced inhibiting effect on the kinetics of membrane binding of 3H3-quinuclidinylbenzilate and 14C-cyclosil in the brain. Cholinesterase reactivator dipyroxime was shown to induce normalization of the cyclosyl specific binding kinetics. It seems to be justified to propose that cooperative action of ... Read more >>

Biull Eksp Biol Med (Biulleten' eksperimental'noi biologii i meditsiny)
[1989, 108(10):459-461]

Cited: 0 times

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In vitro effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on muscarinic cholinergic receptors in mouse striatum.

Y H Suh, M Cho, J I Woo, C W Park,

1. MPTP significantly lowered Kd of the binding of [3H]QNB to muscarine receptor without affecting Bmax values compared with those of control. Hill coefficients (nH) of control and MPTP (250 microM) added group were 1.15 +/- 0.127 and 0.56 +/- 0.202, respectively. 2. Prior addition of pargyline to MPTP did ... Read more >>

Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol. (Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology)
[1989, 94(2):625-629]

Cited: 1 time

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Effect of repeated administration of manganese on the striatal cholinergic and dopaminergic receptors in the rat.

H N Bhargava,

Previous studies suggest that chronic administration of manganese produces symptoms akin to Parkinson's disease, which is believed to be due to derangement in the central cholinergic and dopaminergic system. In the present study the effect of repeated administration of manganese chloride to male Sprague-Dawley rats on the binding of [3H]spiroperidol ... Read more >>

Toxicol. Lett. (Toxicology letters)
[1987, 37(2):135-141]

Cited: 8 times

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Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs.

Timothy J Shafer, Douglas A Meyer, Kevin M Crofton,

Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the ... Read more >>

Environ. Health Perspect. (Environmental health perspectives)
[2005, 113(2):123-136]

Cited: 179 times

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