hyperalgesia

AP-18 is a potent and selective TRPA1 inhibitor. AP-18 inhibits activation of TRPA1 induced by 50 μM Cinnamaldehyde with an IC50 of 3.1 μM and 4.5 μM for human and mouse TRPA1, respectively. AP-18 could reverse complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia in mice. AP-18 could attenuate Yo-Pro uptake induced by 30 μM AITC in a concentration-dependent manner (IC50= 10.3 μM).

AT-121 is a dual μ-opioid and neuropeptide receptor partial agonist (Kis 16.49 and 3.67 nM, respectively). It stimulates [35S]GTPγS binding to cell membranes expressing either μ-opioid receptors or neuropeptide receptors (EC50s of 19.6 and 34.7 nM, respectively.) AT-121 (0.003-0.03 mg kg) reduced capsaicin-induced thermal anisocoria in a dose-dependent manner, but did not increase scratching activity in rhesus monkeys. In rhesus monkey drug self-administration tests, AT-121 at doses of 0.3 to 10 μg kg per injection lacked reinforcing effects (a potential marker of abuse) and did not reduce the reinforcing effects of food pellets.AT-121 (0.01 or 0.03 mg kg) did not induce hyperalgesia, a marker of tolerance, in rhesus monkeys.AT-121 is a safe non-addictive pain reliever with anti-injury and analgesic effects.

1. Methyl eugenol (4-allylveratrole) is a natural constituent of the essential oils of a number of plants widely used in foodstuffs as flavouring agents, in view of the carcinogenic potential of ME, the need to check its presence in food products with effective analytical methods. 2. Methyleugenol has insecticidal properties. 3. Methyleugenol can inhibit the production of nitric oxide and decreased the protein expression of inducible nitric oxide synthase, it down-regulates the production of pro-inflammatory cytokines in the ischemic brain as well as in immunostimulated mixed glial cells; indicates that methyleugenol could be useful for the treatment of ischemia inflammation-related diseases. 4. Methyleugenol has cytotoxicity and genotoxicity. 5. Intravenous (i.v.) treatment with methyleugenol (ME) in either anesthetized or conscious rats elicits hypotension, an effect that seems related to an active vascular relaxation rather than withdrawal of sympathetic tone. 6. Methyleugenol has antinociceptive effect on the second phase of formalin-induced pain, may be due to the inhibition of N-methyl-d-aspartic acid (NMDA) receptor-mediated hyperalgesia via GABA(A) receptors. 7. Methyleugenol has elaxant and antispasmodic actions on guinea-pig isolated ileum.

1. Poncirin (Isosakuranetin-7-neohesperidoside) shows a significant in vitro inhibitory effect on the growth of the human gastric cancer cells, SGC-791, in a dose-dependent manner. 2. Poncirin prevents adipogenesis, enhances osteoblast differentiation in mesenchymal stem cellsincreased bone mineral density, and improves trabecular microarchitecture likely reflect increases bone formation and decreases bone resorption in GIO mice.

The ED50 of J-2156 in rats for the relief of mechanical allodynia and mechanical hyperalgesia in the ipsilateral hindpaws was 3.7 and 8.0 mg kg, respectively. J-2156 is a high potent, selective somatostatin receptor type 4 (SST4 receptor) agonist with IC5

(R)-Mirtazapine ((R)-Org3770) is the R(-)-enantiomer of Mirtazapine, exhibiting anti-injury sensory properties in an animal model of acute thermal hyperalgesia. It functions as a 5-HT3 receptor antagonist and serves as a potential analgesic.

Bromoenol lactone ((6E)-Bromoenol lactone) is a selective calcium-dependent phospholipase A2 (iPLA2β) and serine protease inhibitor that attenuates nicotine-induced breast cancer cell proliferation and migration, inhibits voltage-gated Ca2+ and transient receptor potential classical channels, and inhibits carrageenan-induced prostaglandin production and hyperalgesia in rat hind paws.

Draflazine is an ENT1 inhibitor. It completely reverses the hypersensitivity in the complete Freund's adjuvant (CFA) model of mechanical hyperalgesia. Draflazine also completely reverses the hypersensitivity of the carrageenan inflammation model of therma

PKR1 antagonist 1 (PC1) is an effective antagonist of PKR1. It alleviates both hyperalgesia and allodynia in SNI mice.

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.

AD353 is a selective sigma-1 receptor ligand. It demonstrates high efficacy in models of capsaicin-induced allodynia and PGE2-induced mechanical hyperalgesia. Additionally, AD353 exhibits favorable pharmacokinetic properties.

BI-113823 is an orally active and selective bradykinin B1 receptor antagonist. It alleviates mechanical hyperalgesia induced by complete Freund's adjuvant in rats. BI-113823 is applicable for research on chronic inflammatory pain.

SSTR4 agonist5 (Compound 5) is an orally active agonist of the somatostatin receptor 4 (SSTR4) with an EC50 of 0.228 nM. It demonstrates good stability in human rat liver microsomes and can inhibit mechanical hyperalgesia in rat models.

ONO-8130 is an orally available antagonist of EP1 receptor.

PKI 14-22 amide, myristoylated Acetate inhibit cAMP-dependent protein kinase (PKA) and blocks hyperalgesia produced by spinal administration of 8-bromo-cAMP.

5-BDBD is a potent and selective P2X4 receptor antagonist. 5-BDBD inhibits rP2X4R-mediated currents with an IC50 of 0.75 μM. 5-BDBD completely blocked the basal and acute hyperalgesia induced by NTG.

Bioactive metabolite of nociceptin, antagonist of nociceptin-induced hyperalgesia

Nociceptin (1-7) acetate is a potent agonist of opioid receptor-like 1 (ORL1) receptor. Nociceptin (1-7) combines with nociceptin reduces hyperalgesia and has antinociceptive activity.

UNC3230 is a potent, selective, and ATP-competitive PIP5K1C inhibitor with an IC50 of approximately 41 nM. UNC3230 (UNC 3230) also inhibits PIP4K2C.

VU0155041 sodium is a positive allosteric modulator of mGluR4, promoting extinction in male rats and inhibiting the recovery of morphine-induced conditioned place preference. It alleviates hyperalgesia in nerve injury pain models, useful in neurodegenerative disease research.

The group IVA phospholipase A2 (PLA2), known as calcium-dependent cytosolic PLA2 (cPLA2), selectively releases arachidonic acid from membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins and leukotrienes. AX 048 is a potent group IVA cPLA2 inhibitor that demonstrates 50% inhibition of the enzyme at a mole fraction (XI(50)) of 0.022. Pretreatment with AX 048 (ED50 = 1.2 mg/kg) dose-dependently reduces thermal hyperalgesia evoked by carrageenan injection of rat hind paw. At concentrations as high as 30 μM, AX 048 does not inhibit COX activity or interfere with central cannabinoid receptor signaling.

AR-M 1000390 hydrochloride (ARM-390 HCl) , also known as ARM-390, is a low-internalizing nonpeptidic δ-selective opioid receptor agonist; derivative of SNC 80. Does not trigger acute desensitization of the analgesic response; reduces CFA-induced hyperalgesia. Brain penetrant following systemic administration.

1,7-Dihydroxy-2,3-methylenedioxyxanthone exhibits antiulcerogenic, anti-oxidation, and antihyperalgesic activities and can inhibit carrageenan-induced hyperalgesia.

J-2156 TFA is a selective and potent growth inhibitor receptor type 4 (SST4) agonist that acts on the human SST4 receptor (IC50: 0.05 nM) and rat SST4 receptor (IC50: 0.07 nM). J-2156 TFA exhibited anti-inflammatory activity and was able to alleviate mechanical abnormal pain and mechanical hyperalgesia in the rat ipsilateral hind paw.