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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | M'Dahoma, Saïd Gadotti, Vinicius M. Zhang, Fang-Xiong Park, Byeongyeon Nam, Ji Hye Onnis, Valentina Balboni, Gianfranco Lee, Jae Yeol Zamponi, Gerald W. |
| Description | Country affiliation: Canada Author Affiliation: M'Dahoma S ( Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, T2N 4N1, Canada.); Gadotti VM ( Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, T2N 4N1, Canada.); Zhang FX ( Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, T2N 4N1, Canada.); Park B ( Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul, 130-701, Republic of Korea.); Nam JH ( Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul, 130-701, Republic of Korea.); Onnis V ( Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, 09124, Cagliari, Italy.); Balboni G ( Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, 09124, Cagliari, Italy. gbalboni@unica.it.); Lee JY ( Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul, 130-701, Republic of Korea. ljy@khu.ac.kr.); Zamponi GW ( Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, T2N 4N1, Canada. zamponi@ucalgary.ca.) |
| Abstract | T-type channels are important contributors to the initiation and the maintenance of chronic pain states. Blocking T-type channels is therefore a possible therapeutic strategy for relieving pain. Here, we report the Cav3.2 T-type channel blocking action of a previously reported small organic molecule, KYS-05090S. This compound was able to reduce transiently expressed Cav3.2 currents with low micromolar affinity and mediated a hyperpolarizing shift in half-inactivation potential. KYS-05090S was then tested in models of acute and neuropathic pain. KYS-05090S (10 µg/10 µl delivered intrathecally) significantly reduced acute pain induced by formalin in both the tonic and inflammatory phases. Its antinociceptive effect was not observed when delivered to Cav3.2 null-mice revealing a Cav3.2-dependent mechanism. KYS-05090S also reduced neuropathic pain in a model of partial sciatic nerve injury. Those results indicate that KYS-05090S mediates a potent analgesic effect in inflammatory and neuropathic pain through T-type channel modulation, suggesting that its scaffold could be explored as a new class of analgesic compounds. |
| File Format | HTM / HTML |
| ISSN | 00316768 |
| Issue Number | 2 |
| Volume Number | 468 |
| e-ISSN | 14322013 |
| Journal | Pflügers Archiv - European Journal of Physiology |
| Language | English |
| Publisher | Springer |
| Publisher Date | 2016-02-01 |
| Publisher Place | Germany |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Physiology Acute Pain Drug Therapy Analgesics Pharmacology Calcium Channel Blockers Calcium Channels, T-type Metabolism Neuralgia Quinazolines Action Potentials Therapeutic Use Animals Hek293 Cells Humans Male Mice Mice, Inbred C57bl Nociception Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) Clinical Biochemistry |
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