دورية أكاديمية
Evaluation of a novel calcium channel agonist for therapeutic potential in Lambert-Eaton myasthenic syndrome.
| العنوان: | Evaluation of a novel calcium channel agonist for therapeutic potential in Lambert-Eaton myasthenic syndrome. |
|---|---|
| المؤلفون: | Tarr TB; Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA., Malick W, Liang M, Valdomir G, Frasso M, Lacomis D, Reddel SW, Garcia-Ocano A, Wipf P, Meriney SD |
| المصدر: | The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2013 Jun 19; Vol. 33 (25), pp. 10559-67. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Print Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington, DC : Society for Neuroscience Original Publication: [Baltimore, Md.] : The Society, c1981- |
| مواضيع طبية MeSH: | Calcium Channel Agonists/*therapeutic use , Lambert-Eaton Myasthenic Syndrome/*drug therapy , Purines/*therapeutic use , Thiophenes/*therapeutic use, Action Potentials/drug effects ; Adult ; Aged ; Animals ; Cell Line ; Cyclin-Dependent Kinases/antagonists & inhibitors ; Data Interpretation, Statistical ; Electrophysiological Phenomena/drug effects ; Humans ; Mice ; Mice, Transgenic ; Middle Aged ; Neuromuscular Junction/drug effects ; Neurotransmitter Agents/metabolism ; Patch-Clamp Techniques ; Phosphotransferases/metabolism ; Roscovitine |
| مستخلص: | We developed a novel calcium (Ca(2+)) channel agonist that is selective for N- and P/Q-type Ca(2+) channels, which are the Ca(2+) channels that regulate transmitter release at most synapses. We have shown that this new molecule (GV-58) slows the deactivation of channels, resulting in a large increase in presynaptic Ca(2+) entry during activity. GV-58 was developed as a modification of (R)-roscovitine, which was previously shown to be a Ca(2+) channel agonist, in addition to its known cyclin-dependent kinase activity. In comparison with the parent molecule, (R)-roscovitine, GV-58 has a ∼20-fold less potent cyclin-dependent kinase antagonist effect, a ∼3- to 4-fold more potent Ca(2+) channel agonist effect, and ∼4-fold higher efficacy as a Ca(2+) channel agonist. We have further evaluated GV-58 in a passive transfer mouse model of Lambert-Eaton myasthenic syndrome and have shown that weakened Lambert-Eaton myasthenic syndrome-model neuromuscular synapses are significantly strengthened following exposure to GV-58. This new Ca(2+) channel agonist has potential as a lead compound in the development of new therapeutic approaches to a variety of disorders that result in neuromuscular weakness. |
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| معلومات مُعتمدة: | P50 GM067082 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (Calcium Channel Agonists) 0 (GV-58 compound) 0 (Neurotransmitter Agents) 0 (Purines) 0 (Thiophenes) 0ES1C2KQ94 (Roscovitine) EC 2.7.- (Phosphotransferases) EC 2.7.11.22 (Cyclin-Dependent Kinases) |
| تواريخ الأحداث: | Date Created: 20130621 Date Completed: 20130830 Latest Revision: 20211021 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC3685843 |
| DOI: | 10.1523/JNEUROSCI.4629-12.2013 |
| PMID: | 23785168 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1529-2401 |
|---|---|
| DOI: | 10.1523/JNEUROSCI.4629-12.2013 |