Alpha9 nicotinic acetylcholine receptors and the treatment of pain
Chronic pain is a vexing worldwide problem that causes substantial disability and consumes significant medical resources. Although there are numerous analgesic medications, these work through a small set of molecular mechanisms. Even when these medications are used in combination, substantial amount...
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2009
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v78_n7_p693_McIntosh http://hdl.handle.net/20.500.12110/paper_00062952_v78_n7_p693_McIntosh |
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paper:paper_00062952_v78_n7_p693_McIntosh2023-06-08T14:30:36Z Alpha9 nicotinic acetylcholine receptors and the treatment of pain α-Conotoxin Vc1.1 α-Contoxin RgIA Alpha9 nicotinic GABA-B Pain 4 aminobutyric acid B receptor 4 aminobutyric acid B receptor stimulating agent alpha conotoxin alpha conotoxin PeIA alpha conotoxin rgia alpha conotoxin Vc1.1 baclofen calcium channel N type nicotinic receptor nicotinic receptor alpha10 nicotinic receptor alpha9 nicotinic receptor alpha9alpha10 nicotinic receptor alpha9alpha10 blocking agent nicotinic receptor blocking agent omega conotoxin MVIIA unclassified drug absence of side effects allodynia analgesic activity antinociception asthenia central nervous system disease chronic pain clinical trial confusion diabetic neuropathy dose response drug efficacy drug mechanism drug potency drug receptor binding drug safety drug selectivity drug tolerance human hyperalgesia immune response multiple drug dose nerve function nerve injury neuropathic pain nonhuman pain priority journal protein expression receptor upregulation repeated drug dose review sedation side effect single drug dose Analgesics Animals Conotoxins Humans Nicotinic Agonists Nicotinic Antagonists Pain Protein Multimerization Protein Subunits Receptors, GABA-B Receptors, Nicotinic Recombinant Proteins Chronic pain is a vexing worldwide problem that causes substantial disability and consumes significant medical resources. Although there are numerous analgesic medications, these work through a small set of molecular mechanisms. Even when these medications are used in combination, substantial amounts of pain often remain. It is therefore highly desirable to develop treatments that work through distinct mechanisms of action. While agonists of nicotinic acetylcholine receptors (nAChRs) have been intensively studied, new data suggest a role for selective antagonists of nAChRs. α-Conotoxins are small peptides used offensively by carnivorous marine snails known as Conus. A subset of these peptides known as α-conotoxins RgIA and Vc1.1 produces both acute and long lasting analgesia. In addition, these peptides appear to accelerate the recovery of function after nerve injury, possibly through immune mediated mechanisms. Pharmacological analysis indicates that RgIA and Vc1.1 are selective antagonists of α9α10 nAChRs. A recent study also reported that these α9α10 antagonists are also potent GABA-B agonists. In the current study, we were unable to detect RgIA or Vc1.1 binding to or action on cloned GABA-B receptors expressed in HEK cells or Xenopus oocytes. We review the background, findings and implications of use of compounds that act on α9* nAChRs.11* indicates the possible presence of additional subunits. © 2009 Elsevier Inc. All rights reserved. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v78_n7_p693_McIntosh http://hdl.handle.net/20.500.12110/paper_00062952_v78_n7_p693_McIntosh |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
α-Conotoxin Vc1.1 α-Contoxin RgIA Alpha9 nicotinic GABA-B Pain 4 aminobutyric acid B receptor 4 aminobutyric acid B receptor stimulating agent alpha conotoxin alpha conotoxin PeIA alpha conotoxin rgia alpha conotoxin Vc1.1 baclofen calcium channel N type nicotinic receptor nicotinic receptor alpha10 nicotinic receptor alpha9 nicotinic receptor alpha9alpha10 nicotinic receptor alpha9alpha10 blocking agent nicotinic receptor blocking agent omega conotoxin MVIIA unclassified drug absence of side effects allodynia analgesic activity antinociception asthenia central nervous system disease chronic pain clinical trial confusion diabetic neuropathy dose response drug efficacy drug mechanism drug potency drug receptor binding drug safety drug selectivity drug tolerance human hyperalgesia immune response multiple drug dose nerve function nerve injury neuropathic pain nonhuman pain priority journal protein expression receptor upregulation repeated drug dose review sedation side effect single drug dose Analgesics Animals Conotoxins Humans Nicotinic Agonists Nicotinic Antagonists Pain Protein Multimerization Protein Subunits Receptors, GABA-B Receptors, Nicotinic Recombinant Proteins |
| spellingShingle |
α-Conotoxin Vc1.1 α-Contoxin RgIA Alpha9 nicotinic GABA-B Pain 4 aminobutyric acid B receptor 4 aminobutyric acid B receptor stimulating agent alpha conotoxin alpha conotoxin PeIA alpha conotoxin rgia alpha conotoxin Vc1.1 baclofen calcium channel N type nicotinic receptor nicotinic receptor alpha10 nicotinic receptor alpha9 nicotinic receptor alpha9alpha10 nicotinic receptor alpha9alpha10 blocking agent nicotinic receptor blocking agent omega conotoxin MVIIA unclassified drug absence of side effects allodynia analgesic activity antinociception asthenia central nervous system disease chronic pain clinical trial confusion diabetic neuropathy dose response drug efficacy drug mechanism drug potency drug receptor binding drug safety drug selectivity drug tolerance human hyperalgesia immune response multiple drug dose nerve function nerve injury neuropathic pain nonhuman pain priority journal protein expression receptor upregulation repeated drug dose review sedation side effect single drug dose Analgesics Animals Conotoxins Humans Nicotinic Agonists Nicotinic Antagonists Pain Protein Multimerization Protein Subunits Receptors, GABA-B Receptors, Nicotinic Recombinant Proteins Alpha9 nicotinic acetylcholine receptors and the treatment of pain |
| topic_facet |
α-Conotoxin Vc1.1 α-Contoxin RgIA Alpha9 nicotinic GABA-B Pain 4 aminobutyric acid B receptor 4 aminobutyric acid B receptor stimulating agent alpha conotoxin alpha conotoxin PeIA alpha conotoxin rgia alpha conotoxin Vc1.1 baclofen calcium channel N type nicotinic receptor nicotinic receptor alpha10 nicotinic receptor alpha9 nicotinic receptor alpha9alpha10 nicotinic receptor alpha9alpha10 blocking agent nicotinic receptor blocking agent omega conotoxin MVIIA unclassified drug absence of side effects allodynia analgesic activity antinociception asthenia central nervous system disease chronic pain clinical trial confusion diabetic neuropathy dose response drug efficacy drug mechanism drug potency drug receptor binding drug safety drug selectivity drug tolerance human hyperalgesia immune response multiple drug dose nerve function nerve injury neuropathic pain nonhuman pain priority journal protein expression receptor upregulation repeated drug dose review sedation side effect single drug dose Analgesics Animals Conotoxins Humans Nicotinic Agonists Nicotinic Antagonists Pain Protein Multimerization Protein Subunits Receptors, GABA-B Receptors, Nicotinic Recombinant Proteins |
| description |
Chronic pain is a vexing worldwide problem that causes substantial disability and consumes significant medical resources. Although there are numerous analgesic medications, these work through a small set of molecular mechanisms. Even when these medications are used in combination, substantial amounts of pain often remain. It is therefore highly desirable to develop treatments that work through distinct mechanisms of action. While agonists of nicotinic acetylcholine receptors (nAChRs) have been intensively studied, new data suggest a role for selective antagonists of nAChRs. α-Conotoxins are small peptides used offensively by carnivorous marine snails known as Conus. A subset of these peptides known as α-conotoxins RgIA and Vc1.1 produces both acute and long lasting analgesia. In addition, these peptides appear to accelerate the recovery of function after nerve injury, possibly through immune mediated mechanisms. Pharmacological analysis indicates that RgIA and Vc1.1 are selective antagonists of α9α10 nAChRs. A recent study also reported that these α9α10 antagonists are also potent GABA-B agonists. In the current study, we were unable to detect RgIA or Vc1.1 binding to or action on cloned GABA-B receptors expressed in HEK cells or Xenopus oocytes. We review the background, findings and implications of use of compounds that act on α9* nAChRs.11* indicates the possible presence of additional subunits. © 2009 Elsevier Inc. All rights reserved. |
| title |
Alpha9 nicotinic acetylcholine receptors and the treatment of pain |
| title_short |
Alpha9 nicotinic acetylcholine receptors and the treatment of pain |
| title_full |
Alpha9 nicotinic acetylcholine receptors and the treatment of pain |
| title_fullStr |
Alpha9 nicotinic acetylcholine receptors and the treatment of pain |
| title_full_unstemmed |
Alpha9 nicotinic acetylcholine receptors and the treatment of pain |
| title_sort |
alpha9 nicotinic acetylcholine receptors and the treatment of pain |
| publishDate |
2009 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v78_n7_p693_McIntosh http://hdl.handle.net/20.500.12110/paper_00062952_v78_n7_p693_McIntosh |
| _version_ |
1768542966236839936 |