1 The pressor effects of various tertiary and quaternary isoarecaidine esters in both pithed and anaesthetized rats are reported. In order to elucidate the mechanism of action, various experiments were carried out with the quaternary isoarecaidine methyl ester (Q-4-Me). 2 Treatment with mecamylamine, dexetimide, reserpine and phentolamine abolished or reduced the pressor response to Q-4-Me, whereas pretreatment with cocaine gave rise to a prolonged pressor effect. Plasma noradrenaline levels were significantly increased after the infusion of Q-4-Me. 3 From the results it can be concluded that the pressor effects brought about by the quaternary compounds can be attributed to stimulation of nicotinic and muscarinic receptors in sympathetic ganglia. The consequences of interaction with muscarinic receptors predominate over the effects due to minimal interference with nicotinic receptors by the drug.
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Molecules
May 2022
Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, 1090 Vienna, Austria.
The muscarinic acetylcholine receptor family is a highly sought-after target in drug and molecular imaging discovery efforts aimed at neurological disorders. Hampered by the structural similarity of the five subtypes' orthosteric binding pockets, these efforts largely failed to deliver subtype-selective ligands. Building on our recent successes with arecaidine-derived ligands targeting M, herein we report the synthesis of a related series of 11 hydroxylated arecaidine esters.
View Article and Find Full Text PDFCells
July 2021
Department of Biology and Biotechnologies Charles Darwin, Sapienza University of Rome, 00185 Rome, Italy.
Background: Glioblastoma multiforme (GBM) is characterized by several genetic abnormalities, leading to cell cycle deregulation and abnormal mitosis caused by a defective checkpoint. We previously demonstrated that arecaidine propargyl ester (APE), an orthosteric agonist of M2 muscarinic acetylcholine receptors (mAChRs), arrests the cell cycle of glioblastoma (GB) cells, reducing their survival. The aim of this work was to better characterize the molecular mechanisms responsible for this cell cycle arrest.
View Article and Find Full Text PDFInt J Mol Sci
November 2020
Department of Biology and Biotechnologies Charles Darwin, Sapienza University of Rome, 00185 Rome, Italy.
One of the major limits of chemotherapy is depending on the ability of the cancer cells to elude and adapt to different drugs. Recently, we demonstrated how the activation of the M2 muscarinic receptor could impair neuroblastoma cell proliferation. In the present paper, we investigate the possible effects mediated by the preferential M2 receptor agonist arecaidine propargyl ester (APE) on drug resistance in two neuroblastoma cell lines, SK-N-BE and SK-N-BE(2C), a sub-clone presenting drug resistance.
View Article and Find Full Text PDFPLoS One
October 2020
Center of Pharmacological and Botanical Studies (CEFYBO), CONICET, Buenos Aires, Argentine.
Triple negative tumors are more aggressive than other breast cancer subtypes and there is a lack of specific therapeutic targets on them. Since muscarinic receptors have been linked to tumor progression, we investigated the effect of metronomic therapy employing a traditional anti-cancer drug, paclitaxel plus muscarinic agonists at low doses on this type of tumor. We observed that MDA-MB231 tumor cells express muscarinic receptors, while they are absent in the non-tumorigenic MCF-10A cell line, which was used as control.
View Article and Find Full Text PDFJ Cell Physiol
July 2018
Department of Biology and Biotechnologies "Charles Darwin,", Sapienza University of Rome, Rome, Italy.
Mesenchymal stem cells (MSCs), also known as stromal mesenchymal stem cells, are multipotent cells, which can be found in many tissues and organs as bone marrow, adipose tissue and other tissues. In particular MSCs derived from Adipose tissue (ADSCs) are the most frequently used in regenerative medicine because they are easy to source, rapidly expandable in culture and excellent differentiation potential into adipocytes, chondrocytes, and other cell types. Acetylcholine (ACh), the most important neurotransmitter in Central nervous system (CNS) and peripheral nervous system (PNS), plays important roles also in non-neural tissue, but its functions in MSCs are still not investigated.
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