Bloms-Funke, Petra and Schumacher, Michael and Liu, Song and Su, Diya and Li, Jing and Liere, Philippe and Rupprecht, Rainer and Nothdurfter, Caroline and Bahrenberg, Gregor and Christoph, Thomas and Habermann, Christopher and Kneip, Christa and Schroeder, Wolfgang and Tzschentke, Thomas M. and Saunders, Derek (2022) A novel dual mode-of-action anti-hyperalgesic compound in rats which is neuroprotective and promotes neuroregeneration. EUROPEAN JOURNAL OF PHARMACOLOGY, 923: 174935. ISSN 0014-2999, 1879-0712
Full text not available from this repository. (Request a copy)Abstract
Chronic neuropathic pain (CNP) can result from surgery or traumatic injury, but also from peripheral neuropathies caused by diseases, viral infections, or toxic treatments. Opioids, although very effective for acute pain, do not prevent the development of CNP, and are considered as insufficient treatment. Therefore, there is high need for effective and safe non-opioid options to treat, prevent and eventually reverse CNP. A more effective approach to alleviating CNP would constitute a treatment that acts concurrently on various mechanisms involved in relieving pain symptoms and preventing or reversing chronification by enhancing both neuroprotection and neuroregeneration. We have identified and characterized GRT-X (N-[(3-fluorophenyl)-methyl]-1-(2-methoxyethyl)-4-methyl-2oxo-(7-trifluoromethyl)-1H-quinoline-3-caboxylic acid amide), a novel drug which is able to activate both voltage-gated potassium channels of the Kv7 family and the mitochondrial translocator protein 18 kDa (TSPO). The dual mode-of-action (MoA) of GRT-X was indicated in in vitro studies and in vivo in a rat model of diabetic neuropathy. In this model, mechanical hyperalgesia was dose-dependently inhibited. After severe crush lesion of cervical spinal nerves in rats, GRT-X promoted survival, speeded up regrowth of sensory and motor neurons, and accelerated recovery of behavioral and neuronal responses to heat, cold, mechanical and electrical stimuli. These properties may reduce the likelihood of chronification of acute pain, and even potentially relieve established CNP. The absence of a conditioned place preference in rats suggests lack of abuse potential. In conclusion, GRT-X offers a promising preclinical profile with a novel dual MoA.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 18 KDA TSPO; PERIPHERAL BENZODIAZEPINE-RECEPTOR; NEUROPATHIC PAIN; ETIFOXINE; THERAPY; BRAIN; CHANNELS; LIGANDS; ALLOPREGNANOLONE; RECONSTRUCTION; Dual mode-of-action; Kv7 potassium channels; Mitochondrial translocator protein 18 kDa; (TSPO); Chronic neuropathic pain; Neuroregeneration |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jan 2024 12:12 |
| Last Modified: | 26 Jan 2024 12:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58417 |
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