chronic constriction injury

LP-935509 is a selective, brain-permeable, small molecule competitive inhibitor of articulin-2-associated kinase 1 (AAK1) with an IC50 of 3.3 nM and a Ki of 0.9 nM. LP-935509 is a potent inhibitor of BIKE (IC50 of 14 nM) and a moderate inhibitor of GAK (IC50 of 320±40 nM).

GW-406381 is a highly selective COX-2 inhibitor acting peripherally and centrally, reducing spontaneous ectopic discharges in rat sural nerves following chronic compressive injury. It is suitable for studying central sensitisation and inflammatory pain.

Kv7.2/Kv7.3 agonist 1 (Compound 16) is an orally effective agonist for the KV7.2/7.3 channels (KV7.2/7.3 channel/KCNQ2/3) with an EC50 of 1.03 μM. This compound demonstrates analgesic effects in mouse models of chronic constriction injury (CCI) and Streptozotocin-induced diabetic peripheral neuropathy (DPNP), with ED50 values of 12.02 mg/kg and 9.63 mg/kg, respectively.

ASP8477 is a potent and selective FAAH inhibitor. It increases anandamide levels in the brain when administered orally. In rat models of neuropathic and osteoarthritic pain, ASP8477 demonstrates significant efficacy without causing motor coordination issues. A single oral dose of ASP8477 improves thermal hyperalgesia and cold allodynia in rats with chronic constriction nerve injury. Moreover, ASP8477 restores the decreased muscle pressure threshold in a myalgia model induced by reserpine. Research indicates that ASP8477 possesses analgesic effects effective for alleviating neuropathic and functional pain, making its pharmacological properties suitable for chronic pain treatment.

Z-4105 (formula l) is a nootropic compound. It reverses the amnesia effects induced by electroconvulsive shock (ECS) and methylazoxymethanol acetate (MAM), thereby improving learning and memory functions. The compound enhances the activity of the brain's cholinergic system without affecting other neurotransmitter systems. Additionally, Z-4105 significantly alleviates neuropathic pain caused by chronic constriction injury (CCl) in rat sciatic nerve and spinal nerve ligament models. It is utilized in research on neuropathic pain and cognitive dysfunction.

E0199 is an innovative and potent KV7/NaV dual-target modulator that activates KV7 potassium channels, including KV7.2/7.3 (EC50 = 12.78 nM), KV7.2 (EC50 = 0.50 μM), and KV7.5 (EC50 = 27.14 nM), while inhibiting NaV1.7 (IC50 = 0.52 μM), NaV1.8 (IC50 = 0.24 μM), and NaV1.9 (IC50 = 0.16 μM) sodium channels. In a mouse model of chronic constriction injury (CCI) to the sciatic nerve, E0199 demonstrated potent analgesic effects without significant impact on cardiac and skeletal muscle ion channels. E0199 is applicable in studies related to neuropathic pain (NP).

BCFTP is a potent, orally active, and selective positive allosteric modulator of the human Mas-related G protein-coupled receptor X1 (MrgprX1). It selectively enhances MrgprX1 signaling in HEK293 cells. In a humanized MrgprX1 chronic constriction injury (CCI) mouse model, BCFTP alleviates specific neuropathic pain-related behaviors in an MrgprX1-dependent manner. Additionally, BCFTP synergistically enhances the analgesic effects with psychoactive substances in CCI MrgprX1 mice. This compound can be used for research in neuropathic pain.

L-Serine-O-sulfate potassium inhibits serine racemase (Srr). It can alleviate the increase in NO levels, phosphorylation of nNOS at Ser847, PKC-dependent phosphorylation of GluN1 at Ser896, and the development of mechanical allodynia in mice induced by chronic constriction injury (CCI). L-Serine-O-sulfate potassium is utilized in the study of peripheral neuropathy.

GeX-2 is a truncated analogue of αO-conotoxin. It has the ability to activate GABAB receptors and inhibit α9α10nAChR as well as CaV2.2 channels. Additionally, GeX-2 is effective in alleviating pain in a rat model of chronic constriction injury.