AMPA receptors play an important role in the biological consequences of spinal cord injury: Implications for AMPA receptor modulators for therapeutic benefit.

Autor: Witkin JM; Laboratory of Antiepileptic Drug Discovery, Ascension St. Vincent Hospital, Indianapolis, IN, USA; Departments of Neuroscience and Trauma Research, Ascension St. Vincent Hospital, Indianapolis, IN, USA; RespireRx Pharmaceuticals Inc, Glen Rock, NJ, USA. Electronic address: witkinconsult@gmail.com., Radin DP; RespireRx Pharmaceuticals Inc, Glen Rock, NJ, USA., Rana S; Department of Physical Therapy, University of Florida, Gainesville, FL, USA; McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Breathing Research and Therapeutics Center, University of Florida, Gainesville, FL, USA., Fuller DD; Department of Physical Therapy, University of Florida, Gainesville, FL, USA; McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Breathing Research and Therapeutics Center, University of Florida, Gainesville, FL, USA., Fusco AF; Department of Physical Therapy, University of Florida, Gainesville, FL, USA; McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Breathing Research and Therapeutics Center, University of Florida, Gainesville, FL, USA., Demers JC; Indiana University/Purdue University, Indianapolis, IN, USA., Pradeep Thakre P; Department of Physical Therapy, University of Florida, Gainesville, FL, USA; McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Breathing Research and Therapeutics Center, University of Florida, Gainesville, FL, USA., Smith JL; Laboratory of Antiepileptic Drug Discovery, Ascension St. Vincent Hospital, Indianapolis, IN, USA., Lippa A; RespireRx Pharmaceuticals Inc, Glen Rock, NJ, USA., Cerne R; Laboratory of Antiepileptic Drug Discovery, Ascension St. Vincent Hospital, Indianapolis, IN, USA; RespireRx Pharmaceuticals Inc, Glen Rock, NJ, USA; Faculty of Medicine, University of Ljubljana, Zaloška Cesta 4, Ljubljana, Slovenia.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Oct; Vol. 228, pp. 116302. Date of Electronic Publication: 2024 May 18.
DOI: 10.1016/j.bcp.2024.116302
Abstrakt: Spinal cord injury (SCI) afflicts millions of individuals globally. There are few therapies available to patients. Ascending and descending excitatory glutamatergic neural circuits in the central nervous system are disrupted by SCI, making α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) a potential therapeutic drug target. Emerging research in preclinical models highlights the involvement of AMPARs in vital processes following SCI including breathing, pain, inflammation, bladder control, and motor function. However, there are no clinical trial data reported in this patient population to date. No work on the role of AMPA receptors in sexual dysfunction after SCI has been disclosed. Compounds with selective antagonist and potentiating effects on AMPA receptors have benefit in animal models of SCI, with antagonists generally showing protective effects early after injury and potentiators (ampakines) producing improved breathing and bladder function. The role of AMPARs in pathophysiology and recovery after SCI depends upon the time post injury, and the timing of AMPAR augmentation or antagonism. The roles of inflammation, synaptic plasticity, sensitization, neurotrophic factors, and neuroprotection are considered in this context. The data summarized and discussed in this paper document proof of principle and strongly encourage additional studies on AMPARs as novel gateways to therapeutic benefit for patients suffering from SCI. The availability of both AMPAR antagonists such as perampanel and AMPAR allosteric modulators (i.e., ampakines) such as CX1739, that have been safely administered to humans, provides an expedited means of clinical inquiry for possible therapeutic advances.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [AL, JMW, and RC are associated with RespireRx Pharmaceuticals Inc that owns the AMPA receptor potentiators, CX1739and CX717 discussed in this paper].
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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