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Showing 1 to 12 of 48 entries
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Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons.

Frontiers in pharmacology

Iha HA, Kunisawa N, Shimizu S, Tokudome K, Mukai T, Kinboshi M, Ikeda A, Ito H, Serikawa T, Ohno Y.
PMID: 28232801
Front Pharmacol. 2017 Feb 09;8:57. doi: 10.3389/fphar.2017.00057. eCollection 2017.

Nicotinic acetylcholine (nACh) receptors are implicated in the pathogenesis of epileptic disorders; however, the mechanisms of nACh receptors in seizure generation remain unknown. Here, we performed behavioral and immunohistochemical studies in mice and rats to clarify the mechanisms underlying...

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Iha HA, Kunisawa N, Shimizu S, et al. Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons. Front Pharmacol. 2017;8:57doi: 10.3389/fphar.2017.00057.
Iha, H. A., Kunisawa, N., Shimizu, S., Tokudome, K., Mukai, T., Kinboshi, M., Ikeda, A., Ito, H., Serikawa, T., & Ohno, Y. (2017). Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons. Frontiers in pharmacology, 857. https://doi.org/10.3389/fphar.2017.00057
Iha, Higor A, et al. "Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons." Frontiers in pharmacology vol. 8 (2017): 57. doi: https://doi.org/10.3389/fphar.2017.00057
Iha HA, Kunisawa N, Shimizu S, Tokudome K, Mukai T, Kinboshi M, Ikeda A, Ito H, Serikawa T, Ohno Y. Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons. Front Pharmacol. 2017 Feb 09;8:57. doi: 10.3389/fphar.2017.00057. eCollection 2017. PMID: 28232801; PMCID: PMC5298991.
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Role of Nicotinic Acetylcholine Receptor α3 and α7 Subunits in Detrusor Overactivity Induced by Partial Bladder Outlet Obstruction in Rats.

International neurourology journal

Kim HS, Park WJ, Park EY, Koh JS, Hwang TK, Kim JC.
PMID: 25833476
Int Neurourol J. 2015 Mar;19(1):12-8. doi: 10.5213/inj.2015.19.1.12. Epub 2015 Mar 26.

PURPOSE: To investigate the role of α3 and α7 nicotinic acetylcholine receptor subunits (nAChRs) in the bladder, using a rat model with detrusor overactivity induced by partial bladder outlet obstruction (BOO).METHODS: Forty Sprague-Dawley rats were used: 10 were sham-operated...

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Kim HS, Park WJ, Park EY, et al. Role of Nicotinic Acetylcholine Receptor α3 and α7 Subunits in Detrusor Overactivity Induced by Partial Bladder Outlet Obstruction in Rats. Int Neurourol J. 2015;19(1):12-8doi: 10.5213/inj.2015.19.1.12.
Kim, H. S., Park, W. J., Park, E. Y., Koh, J. S., Hwang, T. K., & Kim, J. C. (2015). Role of Nicotinic Acetylcholine Receptor α3 and α7 Subunits in Detrusor Overactivity Induced by Partial Bladder Outlet Obstruction in Rats. International neurourology journal, 19(1), 12-8. https://doi.org/10.5213/inj.2015.19.1.12
Kim, Hyo Sin, et al. "Role of Nicotinic Acetylcholine Receptor α3 and α7 Subunits in Detrusor Overactivity Induced by Partial Bladder Outlet Obstruction in Rats." International neurourology journal vol. 19,1 (2015): 12-8. doi: https://doi.org/10.5213/inj.2015.19.1.12
Kim HS, Park WJ, Park EY, Koh JS, Hwang TK, Kim JC. Role of Nicotinic Acetylcholine Receptor α3 and α7 Subunits in Detrusor Overactivity Induced by Partial Bladder Outlet Obstruction in Rats. Int Neurourol J. 2015 Mar;19(1):12-8. doi: 10.5213/inj.2015.19.1.12. Epub 2015 Mar 26. PMID: 25833476; PMCID: PMC4386486.
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Clinical signs and studies of the site of action of purified larkspur alkaloid, methyllycaconitine, administered parenterally to calves.

The Canadian veterinary journal = La revue veterinaire canadienne

Nation PN, Benn MH, Roth SH, Wilkens JL.
PMID: 17422179
Can Vet J. 1982 Sep;23(9):264-6.

The purified diterpenoid alkaloid, methyllycaconitine was isolated from Delphinium brownii and injected intravenously into beef calves in order to observe the clinical signs. Following injection and depending upon dosage, calves showed a variety of signs; agitation, respiratory difficulty and...

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Nation PN, Benn MH, Roth SH, et al. Clinical signs and studies of the site of action of purified larkspur alkaloid, methyllycaconitine, administered parenterally to calves. Can Vet J. 1982;23(9):264-6
Nation, P. N., Benn, M. H., Roth, S. H., & Wilkens, J. L. (1982). Clinical signs and studies of the site of action of purified larkspur alkaloid, methyllycaconitine, administered parenterally to calves. The Canadian veterinary journal = La revue veterinaire canadienne, 23(9), 264-6.
Nation, P N, et al. "Clinical signs and studies of the site of action of purified larkspur alkaloid, methyllycaconitine, administered parenterally to calves." The Canadian veterinary journal = La revue veterinaire canadienne vol. 23,9 (1982): 264-6.
Nation PN, Benn MH, Roth SH, Wilkens JL. Clinical signs and studies of the site of action of purified larkspur alkaloid, methyllycaconitine, administered parenterally to calves. Can Vet J. 1982 Sep;23(9):264-6. PMID: 17422179; PMCID: PMC1790203.
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Alpha7 Nicotinic Acetylcholine Receptors Play a Predominant Role in the Cholinergic Potentiation of N-Methyl-D-Aspartate Evoked Firing Responses of Hippocampal CA1 Pyramidal Cells.

Frontiers in cellular neuroscience

Bali ZK, Nagy LV, Hernádi I.
PMID: 28928637
Front Cell Neurosci. 2017 Sep 05;11:271. doi: 10.3389/fncel.2017.00271. eCollection 2017.

The aim of the present study was to identify

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Bali ZK, Nagy LV, Hernádi I. Alpha7 Nicotinic Acetylcholine Receptors Play a Predominant Role in the Cholinergic Potentiation of N-Methyl-D-Aspartate Evoked Firing Responses of Hippocampal CA1 Pyramidal Cells. Front Cell Neurosci. 2017;11:271doi: 10.3389/fncel.2017.00271.
Bali, Z. K., Nagy, L. V., & Hernádi, I. (2017). Alpha7 Nicotinic Acetylcholine Receptors Play a Predominant Role in the Cholinergic Potentiation of N-Methyl-D-Aspartate Evoked Firing Responses of Hippocampal CA1 Pyramidal Cells. Frontiers in cellular neuroscience, 11271. https://doi.org/10.3389/fncel.2017.00271
Bali, Zsolt K, et al. "Alpha7 Nicotinic Acetylcholine Receptors Play a Predominant Role in the Cholinergic Potentiation of N-Methyl-D-Aspartate Evoked Firing Responses of Hippocampal CA1 Pyramidal Cells." Frontiers in cellular neuroscience vol. 11 (2017): 271. doi: https://doi.org/10.3389/fncel.2017.00271
Bali ZK, Nagy LV, Hernádi I. Alpha7 Nicotinic Acetylcholine Receptors Play a Predominant Role in the Cholinergic Potentiation of N-Methyl-D-Aspartate Evoked Firing Responses of Hippocampal CA1 Pyramidal Cells. Front Cell Neurosci. 2017 Sep 05;11:271. doi: 10.3389/fncel.2017.00271. eCollection 2017. PMID: 28928637; PMCID: PMC5591832.
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Novel methyllycaconitine analogues selective for the α4β2 over α7 nicotinic acetylcholine receptors.

Bioorganic & medicinal chemistry

Gallagher R, Qudah T, Balle T, Chebib M, McLeod MD.
PMID: 34798380
Bioorg Med Chem. 2021 Dec 01;51:116516. doi: 10.1016/j.bmc.2021.116516. Epub 2021 Nov 10.

Analogues of methyllycaconitine (MLA) based on a (3-ethyl-9-methylidene-3-azabicyclo[3.3.1]nonan-1-yl)methanol template have been designed and synthesised that incorporate the modified ester sidechains distinct from that present in the natural product. Electrophysiology experiments using Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) revealed...

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Gallagher R, Qudah T, Balle T, et al. Novel methyllycaconitine analogues selective for the α4β2 over α7 nicotinic acetylcholine receptors. Bioorg Med Chem. 2021;51:116516doi: 10.1016/j.bmc.2021.116516.
Gallagher, R., Qudah, T., Balle, T., Chebib, M., & McLeod, M. D. (2021). Novel methyllycaconitine analogues selective for the α4β2 over α7 nicotinic acetylcholine receptors. Bioorganic & medicinal chemistry, 51116516. https://doi.org/10.1016/j.bmc.2021.116516
Gallagher, Ryan, et al. "Novel methyllycaconitine analogues selective for the α4β2 over α7 nicotinic acetylcholine receptors." Bioorganic & medicinal chemistry vol. 51 (2021): 116516. doi: https://doi.org/10.1016/j.bmc.2021.116516
Gallagher R, Qudah T, Balle T, Chebib M, McLeod MD. Novel methyllycaconitine analogues selective for the α4β2 over α7 nicotinic acetylcholine receptors. Bioorg Med Chem. 2021 Dec 01;51:116516. doi: 10.1016/j.bmc.2021.116516. Epub 2021 Nov 10. PMID: 34798380.
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Role of the NMDA-receptor in Prepulse Inhibition in the Rat.

International journal of tryptophan research : IJTR

Linderholm K, Powell S, Olsson E, Holtze M, Snodgrass R, Erhardt S.
PMID: 22084584
Int J Tryptophan Res. 2010;3:1-12. doi: 10.4137/ijtr.s4260. Epub 2010 Feb 12.

Kynurenic acid (KYNA) is an endogenous metabolite of tryptophan. Studies have revealed increased brain KYNA levels in patients with schizophrenia. Prepulse inhibition (PPI) is a behavioral model for sensorimotor gating and found to be reduced in schizophrenia. Previous studies...

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Linderholm K, Powell S, Olsson E, et al. Role of the NMDA-receptor in Prepulse Inhibition in the Rat. Int J Tryptophan Res. 2010;3:1-12doi: 10.4137/ijtr.s4260.
Linderholm, K., Powell, S., Olsson, E., Holtze, M., Snodgrass, R., & Erhardt, S. (2010). Role of the NMDA-receptor in Prepulse Inhibition in the Rat. International journal of tryptophan research : IJTR, 31-12. https://doi.org/10.4137/ijtr.s4260
Linderholm, Klas, et al. "Role of the NMDA-receptor in Prepulse Inhibition in the Rat." International journal of tryptophan research : IJTR vol. 3 (2010): 1-12. doi: https://doi.org/10.4137/ijtr.s4260
Linderholm K, Powell S, Olsson E, Holtze M, Snodgrass R, Erhardt S. Role of the NMDA-receptor in Prepulse Inhibition in the Rat. Int J Tryptophan Res. 2010;3:1-12. doi: 10.4137/ijtr.s4260. Epub 2010 Feb 12. PMID: 22084584; PMCID: PMC3195246.
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The protective effect of α7-nACh receptor and its interaction with 5-HT1B/1D receptors in acute intestinal ischemia-reperfusion injury in rats.

Fundamental & clinical pharmacology

Gharishvandi F, Shafaroodi H, Mohammad Jafari R, Abdollahi A, Pasalar P, Dehpour AR.
PMID: 34061415
Fundam Clin Pharmacol. 2021 Jun 01; doi: 10.1111/fcp.12705. Epub 2021 Jun 01.

Over the past decades, great attention has been given to the nervous system modulating effects on the immune response in inflammation-associated injuries, such as acute intestinal ischemia-reperfusion (IR). Recently, we proved the anti-inflammatory and antioxidant effects of 5-hydroxytryptamine (5-HT)1B/1D...

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Gharishvandi F, Shafaroodi H, Mohammad Jafari R, et al. The protective effect of α7-nACh receptor and its interaction with 5-HT1B/1D receptors in acute intestinal ischemia-reperfusion injury in rats. Fundam Clin Pharmacol. 2021;doi: 10.1111/fcp.12705.
Gharishvandi, F., Shafaroodi, H., Mohammad Jafari, R., Abdollahi, A., Pasalar, P., & Dehpour, A. R. (2021). The protective effect of α7-nACh receptor and its interaction with 5-HT1B/1D receptors in acute intestinal ischemia-reperfusion injury in rats. Fundamental & clinical pharmacology, . https://doi.org/10.1111/fcp.12705
Gharishvandi, Fatemeh, et al. "The protective effect of α7-nACh receptor and its interaction with 5-HT1B/1D receptors in acute intestinal ischemia-reperfusion injury in rats." Fundamental & clinical pharmacology vol. (2021). doi: https://doi.org/10.1111/fcp.12705
Gharishvandi F, Shafaroodi H, Mohammad Jafari R, Abdollahi A, Pasalar P, Dehpour AR. The protective effect of α7-nACh receptor and its interaction with 5-HT1B/1D receptors in acute intestinal ischemia-reperfusion injury in rats. Fundam Clin Pharmacol. 2021 Jun 01; doi: 10.1111/fcp.12705. Epub 2021 Jun 01. PMID: 34061415.
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Quercetin Exhibits α7nAChR/Nrf2/HO-1-Mediated Neuroprotection Against STZ-Induced Mitochondrial Toxicity and Cognitive Impairments in Experimental Rodents.

Neurotoxicity research

Singh NK, Garabadu D.
PMID: 34554409
Neurotox Res. 2021 Dec;39(6):1859-1879. doi: 10.1007/s12640-021-00410-5. Epub 2021 Sep 23.

The objective of the present study was to investigate the α7nAChR-mediated Nrf2-dependant protective activity against streptozotocin (STZ)-induced brain mitochondrial toxicity in Alzheimer's disease (AD)-like rats. STZ (3 mg/kg) was injected through an intracerebroventricular route to induce AD-like dementia. Repeated...

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Singh NK, Garabadu D. Quercetin Exhibits α7nAChR/Nrf2/HO-1-Mediated Neuroprotection Against STZ-Induced Mitochondrial Toxicity and Cognitive Impairments in Experimental Rodents. Neurotox Res. 2021;39(6):1859-1879doi: 10.1007/s12640-021-00410-5.
Singh, N. K., & Garabadu, D. (2021). Quercetin Exhibits α7nAChR/Nrf2/HO-1-Mediated Neuroprotection Against STZ-Induced Mitochondrial Toxicity and Cognitive Impairments in Experimental Rodents. Neurotoxicity research, 39(6), 1859-1879. https://doi.org/10.1007/s12640-021-00410-5
Singh, Niraj Kumar, and Garabadu, Debapriya. "Quercetin Exhibits α7nAChR/Nrf2/HO-1-Mediated Neuroprotection Against STZ-Induced Mitochondrial Toxicity and Cognitive Impairments in Experimental Rodents." Neurotoxicity research vol. 39,6 (2021): 1859-1879. doi: https://doi.org/10.1007/s12640-021-00410-5
Singh NK, Garabadu D. Quercetin Exhibits α7nAChR/Nrf2/HO-1-Mediated Neuroprotection Against STZ-Induced Mitochondrial Toxicity and Cognitive Impairments in Experimental Rodents. Neurotox Res. 2021 Dec;39(6):1859-1879. doi: 10.1007/s12640-021-00410-5. Epub 2021 Sep 23. PMID: 34554409.
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Modulation of α7nAchR by Melatonin Alleviates Ischemia and Reperfusion-Compromised Integrity of Blood-Brain Barrier Through Inhibiting HMGB1-Mediated Microglia Activation and CRTC1-Mediated Neuronal Loss.

Cellular and molecular neurobiology

Chen S, Sun Y, Li F, Zhang X, Hu X, Zhao X, Li Y, Li H, Zhang J, Liu W, Zheng GQ, Jin X.
PMID: 34196879
Cell Mol Neurobiol. 2021 Jul 01; doi: 10.1007/s10571-021-01122-2. Epub 2021 Jul 01.

The only food and drug administration (FDA)-approved drug currently available for the treatment of acute ischemic stroke is tissue plasminogen activator (tPA), yet the therapeutic benefits of this drug are partially outweighed by the increased risk of hemorrhagic transformation...

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Chen S, Sun Y, Li F, et al. Modulation of α7nAchR by Melatonin Alleviates Ischemia and Reperfusion-Compromised Integrity of Blood-Brain Barrier Through Inhibiting HMGB1-Mediated Microglia Activation and CRTC1-Mediated Neuronal Loss. Cell Mol Neurobiol. 2021;doi: 10.1007/s10571-021-01122-2.
Chen, S., Sun, Y., Li, F., Zhang, X., Hu, X., Zhao, X., Li, Y., Li, H., Zhang, J., Liu, W., Zheng, G. Q., & Jin, X. (2021). Modulation of α7nAchR by Melatonin Alleviates Ischemia and Reperfusion-Compromised Integrity of Blood-Brain Barrier Through Inhibiting HMGB1-Mediated Microglia Activation and CRTC1-Mediated Neuronal Loss. Cellular and molecular neurobiology, . https://doi.org/10.1007/s10571-021-01122-2
Chen, Shuang, et al. "Modulation of α7nAchR by Melatonin Alleviates Ischemia and Reperfusion-Compromised Integrity of Blood-Brain Barrier Through Inhibiting HMGB1-Mediated Microglia Activation and CRTC1-Mediated Neuronal Loss." Cellular and molecular neurobiology vol. (2021). doi: https://doi.org/10.1007/s10571-021-01122-2
Chen S, Sun Y, Li F, Zhang X, Hu X, Zhao X, Li Y, Li H, Zhang J, Liu W, Zheng GQ, Jin X. Modulation of α7nAchR by Melatonin Alleviates Ischemia and Reperfusion-Compromised Integrity of Blood-Brain Barrier Through Inhibiting HMGB1-Mediated Microglia Activation and CRTC1-Mediated Neuronal Loss. Cell Mol Neurobiol. 2021 Jul 01; doi: 10.1007/s10571-021-01122-2. Epub 2021 Jul 01. PMID: 34196879.
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Effects of nicotinic and muscarinic ligands on embryonic neurones of Periplaneta americana in primary culture: a whole cell clamp study.

Journal of insect physiology

Pichon Y, Guillet JC, Le Guen J, Tiaho F, Van Eyseren I.
PMID: 12769957
J Insect Physiol. 1998 Mar;44(3):227-240. doi: 10.1016/s0022-1910(97)00165-0.

The pharmacological properties of acetylcholine (ACh) receptors of cultured neurones from embryonic cockroach brains were studied using the whole-cell configuration of the patch-clamp technique. More than 90% of the studied neurones responded to ACh by a monophasic inward current,...

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Pichon Y, Guillet JC, Le Guen J, et al. Effects of nicotinic and muscarinic ligands on embryonic neurones of Periplaneta americana in primary culture: a whole cell clamp study. J Insect Physiol. 1998;44(3):227-240doi: 10.1016/s0022-1910(97)00165-0.
Pichon, Y., Guillet, J. C., Le Guen, J., Tiaho, F., & Van Eyseren, I. (1998). Effects of nicotinic and muscarinic ligands on embryonic neurones of Periplaneta americana in primary culture: a whole cell clamp study. Journal of insect physiology, 44(3), 227-240. https://doi.org/10.1016/s0022-1910(97)00165-0
Pichon, Y, et al. "Effects of nicotinic and muscarinic ligands on embryonic neurones of Periplaneta americana in primary culture: a whole cell clamp study." Journal of insect physiology vol. 44,3 (1998): 227-240. doi: https://doi.org/10.1016/s0022-1910(97)00165-0
Pichon Y, Guillet JC, Le Guen J, Tiaho F, Van Eyseren I. Effects of nicotinic and muscarinic ligands on embryonic neurones of Periplaneta americana in primary culture: a whole cell clamp study. J Insect Physiol. 1998 Mar;44(3):227-240. doi: 10.1016/s0022-1910(97)00165-0. PMID: 12769957.
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Cognitive improvements in a rat model with polyunsaturated fatty acids EPA and DHA through α7-nicotinic acetylcholine receptors.

Nutritional neuroscience

Carlos DH, Bibiana Roselly CR, Angel UL, Laura MA, Kenya Karina SR, Jose Manuel CB, Alejandra CS, Gabriela CCE, Estefanía OR, Aracely SM.
PMID: 32840165
Nutr Neurosci. 2020 Aug 25;1-10. doi: 10.1080/1028415X.2020.1809878. Epub 2020 Aug 25.

The α7-nicotinic acetylcholine receptor (α7-nAChR) is a recognized target for the treatment of dementia associated with aging and certain developmental disorders. This study evaluates memory improvement in a rat model by the effects of polyunsaturated fatty acids EPA and...

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Carlos DH, Bibiana Roselly CR, Angel UL, et al. Cognitive improvements in a rat model with polyunsaturated fatty acids EPA and DHA through α7-nicotinic acetylcholine receptors. Nutr Neurosci. 2020;1-10doi: 10.1080/1028415X.2020.1809878.
Carlos, D. H., Bibiana Roselly, C. R., Angel, U. L., Laura, M. A., Kenya Karina, S. R., Jose Manuel, C. B., Alejandra, C. S., Gabriela, C. C. E., Estefanía, O. R., & Aracely, S. M. (2020). Cognitive improvements in a rat model with polyunsaturated fatty acids EPA and DHA through α7-nicotinic acetylcholine receptors. Nutritional neuroscience, 1-10. https://doi.org/10.1080/1028415X.2020.1809878
Carlos, Delgado-Hernández, et al. "Cognitive improvements in a rat model with polyunsaturated fatty acids EPA and DHA through α7-nicotinic acetylcholine receptors." Nutritional neuroscience vol. (2020): 1-10. doi: https://doi.org/10.1080/1028415X.2020.1809878
Carlos DH, Bibiana Roselly CR, Angel UL, Laura MA, Kenya Karina SR, Jose Manuel CB, Alejandra CS, Gabriela CCE, Estefanía OR, Aracely SM. Cognitive improvements in a rat model with polyunsaturated fatty acids EPA and DHA through α7-nicotinic acetylcholine receptors. Nutr Neurosci. 2020 Aug 25;1-10. doi: 10.1080/1028415X.2020.1809878. Epub 2020 Aug 25. PMID: 32840165.
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Activation of α7 Nicotinic Acetylcholine Receptor Decreases On-site Mortality in Crush Syndrome through Insulin Signaling-Na/K-ATPase Pathway.

Frontiers in pharmacology

Fan BS, Zhang EH, Wu M, Guo JM, Su DF, Liu X, Yu JG.
PMID: 27065867
Front Pharmacol. 2016 Mar 29;7:79. doi: 10.3389/fphar.2016.00079. eCollection 2016.

On-site mortality in crush syndrome remains high due to lack of effective drugs based on definite diagnosis. Anisodamine (Ani) is widely used in China for treatment of shock, and activation of α7 nicotinic acetylcholine receptor (α7nAChR) mediates such antishock...

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Fan BS, Zhang EH, Wu M, et al. Activation of α7 Nicotinic Acetylcholine Receptor Decreases On-site Mortality in Crush Syndrome through Insulin Signaling-Na/K-ATPase Pathway. Front Pharmacol. 2016;7:79doi: 10.3389/fphar.2016.00079.
Fan, B. S., Zhang, E. H., Wu, M., Guo, J. M., Su, D. F., Liu, X., & Yu, J. G. (2016). Activation of α7 Nicotinic Acetylcholine Receptor Decreases On-site Mortality in Crush Syndrome through Insulin Signaling-Na/K-ATPase Pathway. Frontiers in pharmacology, 779. https://doi.org/10.3389/fphar.2016.00079
Fan, Bo-Shi, et al. "Activation of α7 Nicotinic Acetylcholine Receptor Decreases On-site Mortality in Crush Syndrome through Insulin Signaling-Na/K-ATPase Pathway." Frontiers in pharmacology vol. 7 (2016): 79. doi: https://doi.org/10.3389/fphar.2016.00079
Fan BS, Zhang EH, Wu M, Guo JM, Su DF, Liu X, Yu JG. Activation of α7 Nicotinic Acetylcholine Receptor Decreases On-site Mortality in Crush Syndrome through Insulin Signaling-Na/K-ATPase Pathway. Front Pharmacol. 2016 Mar 29;7:79. doi: 10.3389/fphar.2016.00079. eCollection 2016. PMID: 27065867; PMCID: PMC4810156.
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