spinal cord injury

SRS16-86 is a novel third-generation ferrostatin, is an inhibitor of ferroptosis.

Chroman 1 is an inhibitor of ROCK2 (IC50: 1 nM).

Gacyclidine (OTO311) is a small molecule N-methyl-D-aspartate (NMDA) receptor antagonist. Local injection of Gacyclidine in the cochlea inhibits salicylate-induced tinnitus and can be used to treat brain injury, spinal cord injury and tinnitus.

Silperisone HCl (RGH-5002) blocks sodium and calcium channels in cells, decreases excitability and contractility of muscle cells, reduces peripheral tone, and acts as a muscle relaxant and peripheral vasodilator. Silperisone HCl is used to treat recurrent painful myoclonus due to spinal cord injury, abnormal hypertonia due to cerebrovascular disease, dystonia symptoms, cone tension syndrome, multiple sclerosis myospasm and myelitis. silperisone is a sodium channel protein type 2 alpha channel blocker. silperisone is an organosilicon similar to tolperisone, an organosilicon compound with centrally acting muscle relaxant properties.

Tirilazad mesylate (U 74006F) is a non-glucocorticoid, lipid peroxidation inhibitor with antiviral and neuroprotective activities. It confines intracellular intramembranous foci, attenuates spinal cord injuries induced by trauma, stroke, and ischemia reperfusion injuries, inhibits toxins in dogs, and is used in the study of neurological disorders.

KCL-286 is an orally available and potent retinoic acid receptor beta agonist for the amelioration of spinal cord injury (SCI).

Peptide5 acetate reduces animal swelling, astrogliosis, and neuronal cell death after spinal cord injury. Peptide5 acetate significantly reduces the degree of spinal cord injury (SCI) in a rodent ex vivo model.

ALLM (Calpain inhibitor II), a potent calpain and cathepsin protease inhibitor, not only prevents neuronal cell death but also enhances chronic neurological function following spinal cord injury (SCI)[1][2].

LY-266097, a selective 5-HT2BR antagonist, effectively reduces tactile hypersensitivity and demonstrates potential therapeutic effects in alleviating pain caused by nerve injury. Additionally, it decreases the upregulation of 5-HT2B receptors in the dorsal root ganglia and spinal cord following nerve damage. Research indicates that LY-266097 may play a potential role in the development of neuropathic pain pathways.

Leplinine (AIT-082, SPI-205) is a neurotrophic agent that may be used to treat Alzheimer's disease and spinal cord injury.

(±)12(13)-DiHOME is the diol form of (±)12(13)-EpOME , a cytochrome P450-derived epoxide of linoleic acid also known as isoleukotoxin. [1] It is formed from 12(13)-EpOME by soluble epoxide hydrolase (sEH) in neutrophils. [2] 12(13)-DiHOME is toxic to Sf21 cells expressing sEH and to lacZ-expressing control cells, unlike isoleukotoxin, which is only toxic to cells containing sEH.[1] [2] Levels of 12(13)-DiHOME are increased in rat spinal cord following burn injury, and it enhances cold tolerance, increases fatty acid uptake into brown adipocytes, and decreases serum triglyceride levels in mice. Levels are also elevated in bronchoalveolar lavage fluid (BALF) in humans following exposure to biodiesel exhaust and in exhaled breath condensate in patients with allergic asthma following allergen exposure.[5] [6] Plasma levels of 12(13)-DiHOME are increased immediately following moderate-intensity exercise in mice and humans, an effect that can be prevented by brown adipose tissue removal in the mouse.[7]

Deltorphin II is a peptide agonist of δ2-opioid receptors.1,2It is selective for δ-opioid receptors over μ- and κ-opioid receptors in radioligand bindings assays (Kis = 0.0033, >1, and >1 μM, respectively) and induces [35S]GTPγS binding in mouse brain membrane preparations (EC50= 0.034 μM). Deltorphin II (0.12 mg/kg) decreases the infarction zone:risk zone ratio in a rat model of myocardial ischemia-reperfusion injury induced by coronary occlusion, an effect that can be reversed by the δ2-opioid receptor antagonist naltriben but not the δ1-opioid receptor antagonist BNTX.3Intrathecal administration of deltorphin II (15 μg/animal) increases latency to withdraw in the paw pressure and tail-flick tests in rats.4 1.Raynor, K., Kong, H., Chen, Y., et al.Pharmacological characterization of the cloned κ-, δ-, and μ-opioid receptorsMol. Pharm.45(2)330-334(1994) 2.Scherrer, G., Befort, K., Contet, C., et al.The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: A parallel study of mu, delta and combinatorial opioid receptor knockout miceEur. J. Neurosci.19(8)2239-2248(2004) 3.Maslov, L.N., Barzakh, E.I., Krylatov, A.V., et al.Opioid peptide deltorphin II simulates the cardioprotective effect of ischemic preconditioning: role of δ2-opioid receptors, protein kinase C, and KATP channelsBull. Exp. Biol. Med.149(5)591-593(2010) 4.Labuz, D., Toth, G., Machelska, H., et al.Antinociceptive effects of isoleucine derivatives of deltorphin I and deltorphin II in rat spinal cord: A search for selectivity of delta receptor subtypesNeuropeptides32(6)511-517(1998)

Connexin43 mimetic peptide. Reduces swelling, astrogliosis, neuroinflammation and neuronal cell death following spinal cord injury ex vivo and in vivo. Exhibits analgesic effects in models of neuropathic pain. O'Carroll et al (2008) Connexin 43 mimetic peptides reduce swelling, astrogliosis and neuronal cell death after spinal cord injury. Cell.Commun.Adhes. 15 27 PMID:18649176 |Mao et al (2017) Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats. Exp.Brain.Res. 235 3033 PMID:28725925 |Kim et al (2017) Characterising the mode of action of extracellular Connexin43 channel mimetic peptides in an in vitro ischemia injury model. Biochem.Biophys.Acta. 1861 68 PMID:27816754 |Tonkin et al (2017) Attenuation of mechanical pain hypersensitivity by treatment with Peptide5, a connexin-43 mimetic peptide, involves inhibition of NLRP3 inflammasome in nerve-injured mice. Exp.Neurol. 300 1 PMID:29055716

Cyclo(L-Phe-L-Val) is a metabolite of the sponge bacterium Pseudoalteromonas sp. NJ6-3-1, capable of autoinducing the production of antibacterial substances active against S. aureus at low cell density. It induces neurite outgrowth and branching of chick cortical neurons in vitro at concentrations of 16 and 32 μM, increases phosphorylation of the PI3K substrate Akt, and this induction can be blocked by the PI3K inhibitor LY294002. Additionally, it enhances axon sprouting of calcitonin gene-related protein positive (CGRP+) primary afferents in the spinal cord post-crush injury and of serotonin neurons in the uninjured spinal cord. Cyclo(L-Phe-L-Val) is also a bitter taste component of cocoa and roasted coffee.

Methoctramine is a selective antagonist of M2 muscarinic acetylcholine receptors (IC50 = 6.1 nM in CHO-K1 cell membranes).[1] It is selective for M2 over M1, M3, M4, and M5 receptors (IC50s = 92, 770, 260, and 217 nM, respectively). In vitro, methoctramine inhibits acetylcholine-induced reductions in isolated guinea pig tracheal tube contractions when used at a concentration of 1 μM.[2] In vivo, methoctramine inhibits bradycardia and bronchoconstriction induced by acetylcholinein guinea pigs with ED50 values of 38 and 81 nmol/kg, respectively. In a rat model of spinal cord injury, methoctramine suppresses bladder overactivity induced by the non-selective muscarinic acetylcholine receptor agonist oxotremorine M.[3]

Z-LEHD-FMK TFA is a specific and irreversible inhibitor of caspase-9, providing protection against detrimental reperfusion injury and moderating apoptosis, with demonstrated neuroprotective potential in a rat model of spinal cord trauma.

NS309 is a nonselective activator of small- and intermediate-conductance Ca2+-activated K+ (SK KCa2 and IK KCa3.1) channels (EC50s range from 0.12-1.2 µM for SK channels and 10-90 nM for IK channels). It can also activate voltage-gated Kv11.1 channels (hE

Tirilazad, a nonglucocorticoid 21-aminosteroid, serves to inhibit lipid peroxidation. It mitigates the effects of trauma-induced brain or spinal cord injury, as well as damage resulting from stroke, ischemia, and reperfusion injury. Additionally, Tirilazad exhibits antiviral properties against nCoV and offers neuroprotection in cases of ischemic stroke. It is also utilized in subarachnoid hemorrhage research [1] [2] [3].

Hyp9, a specific agonist for the transient receptor potential canonical 6 (TRPC6) channel, is utilized in spinal cord injury (SCI) research [1].

Peptide5 TFA, a connexin 43 mimetic peptide, mitigates swelling, astrogliosis, and neuronal cell death in animal models of spinal cord injury, and suppresses the NLRP3 inflammasome, functioning as an anti-inflammatory agent (1) (2) (3).

PTPσ Inhibitor ISP is a compound that binds to recombinant human PTPs, thereby inhibiting PTPσ signaling. It has the capability to penetrate membranes and counteract the inhibitory effects of chondroitin sulfate proteoglycan (CSPG) on axonal sprouting in spinal cord injury models. Additionally, it fosters remyelination in lysolecithin (LPC)-induced demyelinated spinal cords and supports the migration and maturation of oligodendrocyte progenitor cells (OPCs), enhancing remyelination and functional recovery in Multiple Sclerosis (MS) animal models [1] [2].

Unasnemab (MT-3921), a humanized IgG1 monoclonal antibody, targets repulsive guidance molecule A (RGMa) to enhance locomotor function and support neuroregeneration, showing potential for spinal cord injury research [1].

Phenylbenzothiazole-PEG4-OH (compound 1) shows therapeutic potential for spinal cord injury and may enhance spine formation [1].

C3bot(154-182) TFA, a C3 peptide, facilitates spinal cord injury recovery by promoting regenerative growth of descending fiber tracts. It serves as a potential therapeutic agent to support axonal protection and or repair, alongside functional recovery following traumatic central nervous system (CNS) injury [1].