A Comparison of the α235 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain
Joint Authors
Jinks, John
Mace, Hannah
Ivarsson, Magnus
Richardson, Denise
Ward, Cameron
Edye, Michelle
Gurrell, Rachel
Pitcher, Tom
Young, Kimberly
Rees, Huw
Kinloch, Ross
Nicholson, Janet
McMurray, Gordon
Fish, Rebecca
Bell, Christine
Nickolls, Sarah
Moss, Andrew
Tanimoto-Mori, Sachi
Sweatman, Catherine
Source
Advances in Pharmacological Sciences
Issue
Vol. 2011, Issue 2011 (31 Dec. 2011), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2011-11-28
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
GABAA receptors containing α2/3 subunits are current targets in the battle to develop new pain medications, as they are expressed in the spinal cord where increasing inhibitory drive should result in analgesia.
However, this approach is prone to a range of side effects including sedation, cognitive impairment, and abuse as a consequence of the widespread influence of GABA.
The ability to make subtype selective low-efficacy benzodiazepine compounds, which potentiate the action of GABA at specific α subunits, has the potential to reduce this side effect profile.
In this study, we have investigated the effects of the medium-efficacy positive allosteric modulator (PAM) L-838,417 and the low-efficacy PAM TPA023 in a number of preclinical inflammatory and neuropathic pain models.
We conclude that either the higher level of efficacy at α2/3 or efficacy at α5 is required for compounds to have a significant analgesic effect in a range of models, and, therefore, although the side-effect profile of compounds can be reduced compared to typical benzodiazepines, it is unlikely that it can be completely eliminated.
American Psychological Association (APA)
Nickolls, Sarah& Mace, Hannah& Fish, Rebecca& Edye, Michelle& Gurrell, Rachel& Ivarsson, Magnus…[et al.]. 2011. A Comparison of the α235 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain. Advances in Pharmacological Sciences،Vol. 2011, no. 2011, pp.1-12.
https://search.emarefa.net/detail/BIM-484790
Modern Language Association (MLA)
Nickolls, Sarah…[et al.]. A Comparison of the α235 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain. Advances in Pharmacological Sciences No. 2011 (2011), pp.1-12.
https://search.emarefa.net/detail/BIM-484790
American Medical Association (AMA)
Nickolls, Sarah& Mace, Hannah& Fish, Rebecca& Edye, Michelle& Gurrell, Rachel& Ivarsson, Magnus…[et al.]. A Comparison of the α235 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain. Advances in Pharmacological Sciences. 2011. Vol. 2011, no. 2011, pp.1-12.
https://search.emarefa.net/detail/BIM-484790
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-484790