nociceptive

Zolmitriptan (311C90) selectively binds to and activates serotonin (5-HT) 1B receptors expressed in intracranial arteries and 5-HT 1D receptors located on peripheral trigeminal sensory nerve terminals in the meninges and central terminals in brainstem sensory nuclei. Zolmitriptan is a member of the triptan class of agents with anti-migraine properties. Receptor binding results in constriction of cranial vessels, reduction of vessel pulsation and inhibition of nociceptive transmission, thereby providing relief of migraine headaches. Zolmitriptan may also relieve migraine headaches by inhibition of pro-inflammatory neuropeptide release.

beta-Escin is a natural mixture of triterpenoid saponins isolated from horse chestnut (Aesculus hippocastanum) seeds, can be used as a vasoprotective anti-inflammatory, anti-edematous and anti-nociceptive agent.

Vanillyl Alcohol (3-Methoxy-4-hydroxybenzyl alcohol) possesses anti-angiogenic, anticonvulsive, anti-inflammatory, anti-oxidant, neuroprotective, and anti-nociceptive activities. Vanillyl alcohol can effectively inhibit the cytotoxicity and improved cell viability in 1-methyl-4-phenylpyridinium (MPP+)-induced MN9D dopaminergic cells, it also can attenuate the elevation of reactive oxygen species (ROS) levels, decrease in the Bax/Bcl-2 ratio and poly (ADP-ribose) polymerase proteolysis.

ABT-963 is a potent and selective inhibitor of disubstituted pyridazinone cyclooxygenase-2 (LOX2) that dose-dependently reduces injury perception in a carrageenan model of nociceptive sensitization.ABT-963 is used in the study of arthritis.

Substance P (1-7) 2TFA(68060-49-1(free base)) is the major bioactive metabolite formed after proteolytic degradation of the tachykinin substance P (SP),with anti-inflammatory, anti-nociceptive and anti-hyperalgesic effects

Emorfazone (PH011085) has an anti-nociceptive effect.

Palvanil (Hexadecanamide) is a fast desensitizing agonist of TRPV1. it may be promising agents in the therapy of IBS since it modulates intestinal motility and reduces visceral pain.

Azadiradione (AZD) (AZD) from the methanolic extract of seeds of Azadirachta indica

QX 314 (Lidocaine N-ethyl bromide) is a blocker of non-membrane-permeable,and Inhibits Acid-Induced Activation of Esophageal Nociceptive C Fiber Neurons.

CGP 29030A is a new piperazine derivative with analgesic activity and significant inhibitory effect on potentially nociceptive dorsal horn neurons, which can be used to study painful disorders.

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).

Dihydrocapsaicin (CCRIS1589) is isolated from Capsicum fruit. Capsaicin is the primary active component of the heat and pain-eliciting lipid soluble fraction of the Capsicum pepper. Like capsaicin, dihydrocapsaicin is an irritant. Capsaicin is found in natural hot pepper extracts along with a number of impurities, including dihydrocapsaicin and several lesser impurities. Separation by HPLC is required in order to obtain pure dihydrocapsaicin. Dihydrocapsaicin represents about 10% of the compound present in commercial preparations purporting to be pure capsaicin, but it has about the same pungency as capsaicin. VR1 (vanilloid receptor 1) is a heat activated calcium ion channel which functions as a part of the normal nociceptive pain pathway. Capsaicin elicits a sensation of burning pain by activation of VR1 on small, non-myelinated polymodal C-type nociceptive nerve fibers. The potency of dihydrocapsaicin at VR1 appears equivalent to capsaicin. Antioxidant. Reduces oxidation of serum lipids. Mutagenic. Dihydrocapsaicin is an activator of VR1.

Ziconotide Acetate (107452-89-1 free base) (Prialt) is an analgesic agent and has been used to treat neuropathic and non-neuropathic pain. Ziconotide Acetate (107452-89-1 free base) acts by binding to N-type calcium channels situated on the terminal part of primary afferent neurons of the nociceptive pathway therefore reducing synaptic transmission with potent antinociceptive effects.

1. Vitexin has antinociceptive and antispasmodic activities. 2. Vitexin exhibits a prominent first-pass effect. 3. Vitexin has antioxidant, antimyeloperoxidase, and α-glucosidase inhibitory activities. 4. Vitexin can either inhibit or induce activities of

1. Bullatine A, a diterpenoid alkaloid of the genus Aconitum, possesses anti-rheumatic, anti-inflammatory and anti-nociceptive effects, may be used for the treatment of neurodegenerative diseases such as arthritis.

CRMP2-Ubc9-NaV1.7 inhibitor 194, is a CRMP2-Ubc9-NaV1.7 inhibitor.

Oxysophocarpine is an alkaloid extracted from seaweed. It has neuroprotective and antinociceptive effects on the central and peripheral nervous systems.

AMTB hydrochloride (AMTB HCl) is a novel TRPM8 channel blocker and is effective for pain and urinary diseases. AMTB can act on the bladder afferent pathway to attenuate the bladder micturition reflex and nociceptive reflex responses in the rat.

Alosetron hydrochloride (GR 68755) is the hydrochloride salt form of alosetron, a potent and selective 5-HT3 receptor antagonist. Alosetron blocks the actions of serotonin at 5-HT3 sites in the peripheral nervous system, particularly on enteric and nociceptive sensory neurons, thereby affecting the regulation of visceral pain, decreasing gastrointestinal contraction and motility, and decreasing gastrointestinal secretions.

σ1 Receptor antagonist-1 is a selective σ1 receptor antagonist.

BAY-1797 is an orally active and selective P2X4 antagonist (IC50: 211 nM against human P2X4) with anti-nociceptive and anti-inflammatory effects. BAY-1797 displays no or very weak activity on the other P2X ion channels.

PDE7-IN-3 (Example 2) serves as an inhibitor of phosphodiesterase PDE7 and exhibits potential analgesic properties. It is applicable in the research of various pain types including inflammatory, neuropathic, visceral, and nociceptive pain [1].

ASIC blocker (IC50 values are 0.44, 2.1 μM and no effect at rat ASIC1a, ASIC3 and ASIC2a, respectively: IC50 value = 0.12 μM at human ASIC1a with no effect at ASIC2a or ASIC3). Inhibition was also observed at heteromeric ASIC channels (IC50 values are 0.79, 0.87 and 4.5 uM at rat ASIC1a+3, ASIC1a+2a and ASIC2a+3; IC5O values are 0.33 and 0.69 uM at human ASIC1a+2a and ASIC1a+3, with no effect at ASIC2a+3). Attenuates pathophysiological nociceptive behaviors in CFA-inflamed and CCI rats.

3-Carene（Delta-3-Carene） is a bicyclic monoterpene extracted from western larch and Douglas-fir that acts as a phytofungicide.3-Carene inhibits inflammatory infiltrates and COX-2 overexpression induced by nociceptive stimuli.3-Carene has anti-injury properties and promotes the activity and expression of alkaline phosphatase, an early marker of osteoblast differentiation.

Potent and selective, voltage-dependent R-type CaV2.3 calcium channel blocker (IC50 = 30 nM). Antinociceptive; inhibits nociceptive C-fibre and Aδ-fibre-evoked neuronal responses.

Efipladib is a phospholipase inhibitor. Efipladib decreases nociceptive responses without affecting PGE2 levels in the cerebral spinal fluid.

AC-099 hydrochloride is a selective full agonist of the neuropeptide FF2 receptor NPFF2R (EC50=1189 nM) and partial agonist function of the neuropeptide FF1 receptor NPFF1R (EC50=2370 nM) that reverses opioid-induced nociceptive sensitization, and may be used to study neurological....

AZD8797 (KAND567) is an orally available, selective and potent human CX3CR1-converting antagonist with inhibitory effects on CX3CR1 and CXCR2, and potentially protects against SARS-CoV-2-induced neuronal damage, preventing worsening of nociceptive sensitization and microglial activation in a migraine model of rats following seizures.

Hexahydrofarnesyl acetone (Phytone) enhanced both the sticky materials production and cell growth, plays some role in the increase of sticky materials and cell growth.

Endothelin receptor agonist (EC50 values are 7.5 and > 150 nM for contraction of pig coronary artery and guinea pig aorta respectively). Nociceptive in vivo.

Fursultiamine (Alinamin F) is a disulfide derivative of thiamine, or an allithiamine. It has potential uses in the treatment of vitamin B1 deficiency.

Vincristine binds to tubulin and inhibits the formation of microtubules, thereby inhibiting mitosis of the cancer cell. Vincristine can be used as a microtubule-destabilizing agent for research on the treatment of hematologic cancers, such as leukemia and

SSTR4 agonist 4 is a potent SSTR4 agonist with potential applications in pain research. SSTR4 agonists demonstrate efficacy in rodent models of pain associated with acute and chronic anti-peripheral nociceptive and anti-inflammatory activity. SSTR4 is expressed at relatively high levels in the hippocampus and neocortex, regions involved in memory and learning, and in Alzheimer's disease pathology [1].

Sigma-1 receptor antagonist 5 (compound 12), a 4-pyridylpiperidine derivative, exhibits analgesic properties through its antagonistic action on sigma receptors (Ki=4.5 nM (σ1R), 10 nM (σ2R)) and the histamine H3 receptor (hH3R, Ki=7.7 nM, IC50=215 nM). It effectively attenuates Capsaicin-induced nociception and demonstrates significant antinociceptive effects in both nociceptive and neuropathic pain models [1].

Sophocarpine, a major ingredient of Sophora alopecuroides, has a wide range of pharmacological effects.

Dolcanatide, an orally active guanylate cyclase-C (GC-C) agonist, exhibits laxative, anti-nociceptive, and anti-inflammatory properties. It is utilized in research concerning inflammatory bowel disease [1] [2].

SB-612111 hydrochloride is a potent, novel orphan receptor for opioid receptors (ORL-1) antagonist with high affinity for hORL-1 and a Ki value of 0.33 nM. SB-612111 hydrochloride is able to act on mu-receptor (Ki: 57.6 nM), κ SB-612111 hydrochloride effectively antagonized the nociceptive effects of Nociceptin in an acute pain model.

The acyl amides are a family of endogenous lipids that act as potent modulators of pain and inflammation. The best characterized members of this family are the arachidonoyl amides, which includes N-arachidonoyl ethanolamide (AEA; anandamide). N-palmitoyl glycine (PalGly) contains an 18-carbon saturated fatty acid that is amide-linked to glycine and is structurally similar to the phospholipid-derived N-acyl ethanolamines. Endogenously produced in rat skin and spinal cord, PalGly is present in 100-fold greater amounts in skin and 3-fold greater in brain compared to AEA. Injection of 0.43 μg PalGly in rat hindpaw inhibits heat-induced firing of nociceptive neurons in rat dorsal horn. PalGly treatment induces transient calcium influx in native dorsal root ganglion (DRG) cells and in the PTX-sensitive, DRG-like cell line F-11 (EC50 = 5.5 μM).

SSTR4 agonist 2 is a potent somatostatin receptor subtype 4 (SSTR4) agonist with potential applications in research on SSTR4-related medical disorders. The SSTR4 pathway inhibits nociceptive and inflammatory processes [1].

C3001a is a selective activator for TREK, against other two-pore domain K+(K2P) channels. C3001a binds to the cryptic binding site formed by P1 and TM4 in TREK-1. C3001a targets TREK channels in the peripheral nervous system to reduce the excitability of nociceptive neurons. In neuropathic pain, C3001a alleviated spontaneous pain and cold hyperalgesia. In a mouse model of acute pancreatitis, C3001a alleviated mechanical allodynia and inflammation. C3001a represents a lead compound which could advance the rational design of peripherally acting analgesics targeting K2P channels without opioid-like adverse effects.

Neuromedin U-23 (NMU-23) is a neuropeptide involved in diverse biological processes, including smooth muscle contraction, energy homeostasis, and nociception.1It is an agonist of neuromedin-U receptor 1 (NMUR1; EC50= 0.17 nM for the human receptor in a calcium mobilization assay using HEK293 cells) and NMUR2 (EC50= ~1.4-2 nM for arachidonic acid release in CHO cells expressing the human receptor).2,3NMU-23 (1 μM) induces contractions in isolated rat colon smooth muscle strips.4It decreases body weight and food intake and increases core body temperature in mice when administered at a dose of 36 μg/animal.5Intrathecal administration of NMU-23 decreases the mechanical pain threshold in the von Frey test in rats.6 1.Mitchell, J.D., Maguire, J.J., and Davenport, A.P.Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin SBr. J. Pharmacol.158(1)87-103(2009) 2.Szekeres, P.G., Muir, A.I., Spinage, L.D., et al.Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3J. Biol. Chem.275(27)20247-20250(2000) 3.Hosoya, M., Moriya, T., Kawamata, Y., et al.Identification and functional characterization of a novel subtype of neuromedin U receptorJ. Biol. Chem.275(38)29528-29532(2000) 4.Brighton, P.J., Wise, A., Dass, N.B., et al.Paradoxical behavior of neuromedin U in isolated smooth muscle cells and intact tissueJ. Pharmacol. Exp. Ther.325(1)154-164(2008) 5.Peier, A., Kosinski, J., Cox-York, K., et al.The antiobesity effects of centrally administered neuromedin U and neuromedin S are mediated predominantly by the neuromedin U receptor 2 (NMUR2)Endocrinology150(7)3101-3109(2009) 6.Yu, X.H., Cao, C.Q., Mennicken, F., et al.Pro-nociceptive effects of neuromedin U in ratNeuroscience120(2)467-474(2003)

N(G)-Nitroarginine-4-nitroanilide is an anti-nociceptive in mice.

Ziconotide TEA acts by binding to N-type calcium channels situated on the terminal part of primary afferent neurons of the nociceptive pathway therefore reducing synaptic transmission with potent antinociceptive effects.

Salvinorin A propionate is a selective partial agonist at κ1-opioid receptors (KOR) with a Ki value of 32.6 nM. It inhibits adenylate cyclase (EC50 = 4.7 nM) in HEK293 cells transfected with human KOR. It is selective for KORs over μ, δ, and ORL-1 opioid receptors and has no effect at serotonin, dopamine, muscarinic, or adrenergic receptors. In mice, salvinorin A propionate (13 μg, i.c.v.) reduces nociceptive responses in a radiant heat tail-flick assay, though not as potently as salvinorin A .

(S)-Mirtazapine ((S)-Org3770) is the S(+)-enantiomer of Mirtazapine, functioning as a selective 5-HT2 receptor antagonist with pro-nociceptive effects. It is commonly used in combination with the R(-)-enantiomer of Mirtazapine to study depression.

Selective galanin GAL2 receptor antagonist (Ki values are 13.1 and 420 nM for GAL2 and GAL1 receptors respectively). Blocks the pro-nociceptive effect of GAL2 receptor agonists.

Prostaglandin F2α serinol amide, a serinolamide G protein-coupled receptor, elevates calcium levels in human non-small cell lung cancer cells. Additionally, Prostaglandin F2α functions as a luteinizing hormone in sheep and potentially serves as a nociceptive mediator in the spinal cord [1] [2] [3].

TFLLR-NH2, reversed amino acid sequence control peptide, is a PAR1 selective agonist that significantly increases the nociceptive threshold.

Umbellulone is a natural product isolated from Umbellularia californica, and stimulates the TRPA1 channel in a subset of peptidergic, nociceptive neurons, activating the trigeminovascular system via this mechanism.

VVZ-149 is an antagonist of both serotonin receptor 2A (5HT2A) and glycine transporter type 2 (GlyT2), with potential anti-nociceptive activity.