BioAssay record AID 179945 submitted by ChEMBL: Inhibition of PI (phospho inositol) response in rat hippocampus by the selective antagonist pirenzepine in the presence of 50 uM concentration of the compound.
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Pirenzepine: An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.
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Telenzepine is a thienobenzodiazepine acting as selective M1 antimuscarinic. It is used in the treatment of peptic ulcers.[1] Telenzepine is atropisomeric, in other words the molecule has a stereogenic C-N-axis. In neutral aqueous solution it displays a half-life for racemization of the order of 1000 years. The enantiomers have been resolved. The activity is related to the (+)-isomer which is about 500-fold more active than the (-)-isomer at muscarinic receptors in the rat cerebral cortex.[2] ...
Pirenzepine (Gastrozepin), an M1 selective antagonist, is used in the treatment of peptic ulcers, as it reduces gastric acid secretion and reduces muscle spasm. It is in a class of drugs known as muscarinic receptor antagonists - acetylcholine being the neurotransmitter of the parasympathetic nervous system which initiates the rest-and-digest state (as opposed to fight-or-flight), resulting in an increase in gastric motility and digestion; whereas pirenzepine would inhibit these actions and cause decreased gastric motility leading to delayed gastric emptying and constipation. It has no effects on the brain and spinal cord as it cannot diffuse through the blood-brain barrier ...
We have, in the accompanying work, demonstrated the coexistence of M2 and M3 muscarinic receptors in the circular smooth muscle of canine colon. In the present study, the effects of muscarinic receptor stimulation on phosphoinositide turnover and adenylate cyclase activity were examined. In myo-[3H]inositol-labeled circular smooth muscle strips, carbachol caused a concentration-dependent (EC50 = 5 microM) increase in [3H]inositol phosphate production. The more M3 receptor-selective muscarinic antagonist pirenzepine (KB = 53 nM) was approximately 60 times more potent than the more M2-selective agent AF-DX 116 (KB = 3 microM) in blocking carbachol-elicited accumulation of [3H]inositol phosphates. The carbachol-stimulated increase in [3H]inositol phosphate accumulation was not affected by pretreatment of the tissue with pertussis toxin (200 ng/ml, 3 hr). Within the first minute, carbachol (100 microM) caused a rapid and transient increase of [3H]inositol 1,4,5-trisphosphate production that ...
Training-induced neuronal activity develops in the mammalian limbic system during discriminative avoidance conditioning. This study explores behaviorally relevant changes in muscarinic ACh receptor binding in 52 rabbits that were trained to one of five stages of conditioned response acquisition. Sixteen naive and 10 animals yoked to criterion performance served as control cases. Upon reaching a particular stage of training, the brains were removed and autoradiographically assayed for 3H-oxotremorine-M binding with 50 nM pirenzepine (OXO-M/PZ) or for 3H-pirenzepine binding in nine limbic thalamic nuclei and cingulate cortex. Specific OXO-M/PZ binding increased in the parvocellular division of the anterodorsal nucleus early in training when the animals were first exposed to pairing of the conditional and unconditional stimuli. Elevated binding in this nucleus was maintained throughout subsequent training. In the parvocellular division of the anteroventral nucleus (AVp), OXO-M/PZ binding ...
mRNAs encoding five genetically distinct muscarinic ACh receptors are present in the CNS. Because of their pharmacological similarities, it has not been possible to detect the individual encoded proteins; thus, their physiological functions are not well defined. To characterize the family of proteins, a panel of subtype-selective antibodies was generated against recombinant muscarinic receptor proteins and shown to bind specifically to each of the cloned receptors. Using immunoprecipitation, three receptor proteins (m1, m2, and m4) accounted for the vast majority of the total solubilized muscarinic binding sites in rat brain. These receptor subtypes had marked differences in regional and cellular localization as shown by immunocytochemistry. The m1-protein was present in cortex and striatum and was localized to cell bodies and neurites, consistent with its role as a major postsynaptic muscarinic receptor. The m2-receptor protein was abundant in basal forebrain, scattered striatal neurons, ...
Purpose: : The objectives of this study were: 1) to determine, in vitro, the muscarinic receptor subtype selectivity of 1-[1-(2-Tolyl)-1,4-bipiperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one (TBPB): and 2) to examine, in vivo, its effect on ocular hypotension and miosis. Methods: : Chinese hamster ovary (CHO) cells transfected with plasmid expressing human m1, m3, m4, and m5 were used to determine receptor selectivity of TBPB in a fluorometric imaging plate reader (FLPR) assay. Normotensive Dutch Belted rabbits were used to examine the effects of TBPB on intraocular pressure (IOP) and pupillary size upon topical application. In other studies, rabbits were dosed topically with TBPB in the absence and presence of pirenzepine, AF-DX 116 and 4-DAMP, M1, M2, and M3 receptor selective antagonists, respectively, to confirm the predominant muscarinic receptor subtype responsible for the ocular action of TBPB. Results: : TBPB selectively activated m1 receptors with E-max of 91% compared to carbachol ...
The aim of this study was to identify and elucidate the vasorelaxant activity of echinacoside, a phenylethanoid glycoside isolated from the medicinal herb Cistanche tubulosa, and its possible underlying mechanism on isolated rat thoracic aortic rings pre-contracted with phenylephrine (PE, 1 mu M) and KCI (60 mM). Echinacoside (30-300 mu M) exhibited an acute relaxation in endothelium-intact rings in a concentration-dependent manner, while this relaxation was significantly inhibited in endothelium-denuded condition and in the presence of the endothelial nitric oxide synthase (eNOS) inhibitor, N-w-nitro-L-arginine methyl ester (L-NNA, 100 mu M), an unselective Soluble guanylate cyclase blocker, methylene blue (10 mu M), the selective sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 mu M); in addition, atropine (1 mu M), a selective muscarinic receptor antagonist, partially affected the relaxation. However, the cyclooxygenase inhibitor indomethacin (5 mu M) had no influence on the ...
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TY - JOUR. T1 - Cimetidine, ranitidine, and pirenzepine in the treatment of duodenal ulcer. T2 - A six-month low-dose treatment period followed by a six-month observation period. AU - Leandro, G.. AU - Battaglia, G.. AU - Di Mario, F.. AU - Cozzolongo, R.. AU - Giannuzzi, V.. AU - Cannizzaro, R.. AU - Manghisi, O. G.. AU - Naccarato, R.. PY - 1990. Y1 - 1990. N2 - One hundred twenty-one consecutive patients with healed duodenal ulcer (DU) entered a single-blind, randomized, one-year study. They were treated with either cimetidine 400 mg (41 patients), ranitidine 150 mg (40 patients), or pirenzepine 50 mg (41 patients) at bedtime for the first six months and had no treatment in the subsequent six-month observation period. The patients were well matched in common clinical and biochemical parameters. An upper gastrointestinal endoscopy was performed every three months in all asymptomatic subjects and at every symptomatic relapse. Statistics were calculated by chi-square test with Yates correction, ...
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The effect of long-term ethanol exposure on muscarinic receptors was investigated in human neuroblastoma SH-SY5Y cells. Exposure to 100 mM ethanol for 4 days enhanced both peak and steady-state levels of carbachol-stimulated inositol 1,4,5-bisphosphate increase. An ethanol concentration of 50 mM was sufficient for an enhancement of this event. The carbachol-stimulated decrease in [3H]inositol-labeled [3H]phosphatidylnositol 4,5-bisphosphate and increase [3H]inositol trisphosphate and [3H]inositol bisphosphate were also potentiated in ethanol-treated cells, which demonstrated that the receptor-stimulated activation of phospholipase C is augmented. Experiments with pirenzepine showed that carbachol-stimulated inositol 1,4,5-trisphosphate increase is mediated via M1 receptors both in ethanol-treated and control cells. Ethanol exposure for 2 or 4 days also caused an increase in [3H]N-methylscopolamine and [3H]quinuclidinyl benzilate binding sites and elevation of [3H]pirenzepine binding, which ...
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A recently proposed classification of muscarinic receptor subtypes in based on the regional differences in the affinities of these receptors for selective antagonists and agonists (Hammer and...
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Endogenous Acetylcholine Release Enhances Granule Cell Excitability by Lowering the Action Potential Threshold(Ai) Hippocampal slice preparation schematic and e
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We previously reported that paeoniflorin but not albiflorin, components of peony root, produced ameliorative effects on scopolamine−induced spatial cognitive impairment in rats.In this study, we examined the effects of paeoniflorin and muscarinic receptor antagonists on long−term potentiation(LTP)of population spike recorded from the CA1 region of rat hippocampal slices.Bath applications of an M,SUB,1,/SUB,− and M,SUB,2,/SUB,−receptor antagonist scopolamine and a selective M,SUB,1,/SUB,−receptor antagonist pirenzepine, at a concentration of 10 μM, significantly suppressed LTP, whereas AF−DX116, a selective M,SUB,2,/SUB,−receptor antagonist, failed to affect it.Paeoniflorin(0.1−1μM), which alone was ineffective on LTP induction, significantly reversed the suppressive effects of scopolamine and pirenzepine(10μM).In contrast, albiflorin(0.1−1μM)had no effect on the scopolamine−induced LTP suppression.These results suggest that paeoniflorin reversal of the muscarinic ...
Cholinergc Muscarinic Binding by Human Lymphocytes: Changes with Aging, Antagonist Treatment, and Sende Dementia of the Alzheimer Type - Jose M. Rabey, MD, Louis Shenkman, MD, and Gad M. Gilad, PhD" In peripheral blood lymphocytes (mixed lymphocytes isolated on a Ficoll-Hypaque density gradient) derived from normal human subjects, cholinergic muscarinic binding capacity was found to increase with age. In contrast, lymphocytes derived from patients with "probable" senile dementia of the Alzheimer type (SDAT) exhibited a marked reduction in binding capacity. Treatment of these patients with antimuscarinic drugs was associated with increased muscarinic binding by lymphocytes. These results indicate that cholinergic muscarinic binding by peripheral blood lymphocytes may be useful in the study of alterations associated with aging and SDAT, as well as in evaluating changes induced by certain cholinergic drug treatments. Rabey JM, Shenkman L, Gilad GM: Cholinergic muscarinic binding by human ...
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Several highly selective biochemical markers were used to assess the persistent central cholinergic dysfunction which accompanies administration of the cholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A). Rats received a single bilateral intracerebroventricular injection of AF64A (3 nmol/3 microliter/side) or vehicle and measurements were carried out in the cerebral cortices, hippocampi and corpora striata at 7 and 21 days postinjection. The drug binding sites of muscarinic cholinergic receptors, as revealed by high-affinity binding of (-)-[3H]quinuclidinyl benzilate (a classical muscarinic antagonist), [3H]pirenzepine (a selective antagonist of the putative M1 muscarinic receptor subclass) and (+)-[3H]cis-methyldioxolane (a potent muscarinic agonist), were not significantly affected by AF64A treatment. As reported previously, activity of the cholinergic synthetic enzyme choline acetyltransferase was reduced markedly (60-65%) in the hippocampi of AF64A-treated rats. A similar ...
The results of these experiments in anaesthetised Brown Norway rats show that prolonged inhalation of methacholine results in a predominantly parenchymal (or tissue) constrictor response which is effectively reversed by a maximum dose of atropine sulphate but not by pirenzepine. In contrast, intravenous methacholine produced more marked changes in airway resistance which were reversed by pirenzepine.. Our adaptation of the low frequency forced oscillation technique allows lung mechanics to be partitioned into airway and parenchymal components by fitting the constant phase model to the impedance spectra. The airways through which gas moves by bulk flow will be included in the airway component, whereas airways through which gas moves by diffusion are likely to be included in the parenchymal component. It is therefore most likely that the parenchymal response is the result of contraction of smooth muscle in respiratory bronchioles and alveolar ducts and of contractile elements in the alveolar ...
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