drg neurons

CAY10787 is an oxysterol and a negative allosteric modulator of GABAAreceptors.1,2It reduces GABA-induced currents in HEK cells expressing α1β1γ2or α4β3γ2subunit-containing GABAAreceptors (IC50s = 1.5 and 1 μM, respectively).2CAY10787 (500 nM) reduces GABA-induced depolarization of peptidergic and non-peptidergic nociceptors, C-LTMRs, and cold thermosensors in isolated mouse dorsal root ganglion (DRG) neurons.In vivo, CAY10787 (2, 10, and 50 mg/kg) increases latency to nocifensive behaviors in the hot plate test in mice. 1.Hahn, M., Tang, M., and Subbiah, M.T.Cholest-3,5-dien-7-one formation in peroxidized human plasma as an indicator of lipoprotein cholesterol peroxidation potentialBiochim. Biophys. Acta1255(3)341-343(1995) 2.Niu, C., Leavitt, L.S., Lin, Z., et al.Neuroactive type-A γ-aminobutyric acid receptor allosteric modulator steroids from the hypobranchial gland of marine mollusk, Conus geographusJ. Med. Chem.64(10)7033-7043(2021)

Olodanrigan (EMA401), a highly selective AT2R antagonist, inhibition of augmented AngII/AT2R induced p38 and p42/p44 MAPK activation, and hence inhibition of DRG neuron hyperexcitability and sprouting of DRG neurons. EMA401 blocks p38, p42/p44 mitogen-activated protein kinase (MAPK) activation, neurite outgrowth in adult rat DRG neurons, and sensitization of adult rat and human DRG neurons induced by AngII. It inhibits capsaicin responses in cultured hDRG neurons.

ML382 is a potent and selective MrgX1 positive allosteric modulator(EC50 : 190 nM).

Tat-CBD3 is a chemical compound inhibiting the interaction between the N-type voltage-gated calcium channel Cav2.2 and collapsin response mediator protein 2 (CRMP2), as well as the interaction between CRMP2 and the NMDA receptor NR2B subunit. At a concentration of 10 µM, Tat-CBD3 reduces the Cav2.2-CRMP2 interaction by 43% in cell-free assays and impedes the NMDA receptor NR2B subunit-CRMP2 interaction in immunoprecipitation assays. It lowers voltage-induced calcium currents by about 60% in primary rat dorsal root ganglion (DRG) neurons and decreases glutamate-induced cytosolic calcium level rises in primary rat hippocampal neurons. When administered at 20 mg/kg, Tat-CBD3 lessens infarct volume in a rat model of cerebral ischemia following middle cerebral artery occlusion (MCAO). Additionally, intrathecal delivery of Tat-CBD3 at a dose of 20 µg/5 µl mitigates carrageenan-induced thermal hypersensitivity in rats.

WS-12 is a potent TRPM8 agonist that acts as a cooling agent (EC50 : 193 nM)

CSD-CH2(1,8)-NH2 is a selective and competitive kappa-opioid receptor (KOR) antagonist with a K i of 6.8 nM. It inhibits calcium mobilization in dorsal root ganglion (DRG) neurons and antagonizes the antinociceptive effect of U50,488, making it useful for research into neuropsychiatric disorders [1].

ω-Conotoxin CVIF is a selective inhibitor of Ca v 2.2 channels, demonstrating an IC50 value of 34.3 nM in isolated rat DRG neurons. Its blockade of Cav2.2 channels is weakly reversible [1].

Tat-AKAP79 (326-336) is a peptide that links the HIV-1 Tat protein transduction domain with an 11-amino acid sequence from A-kinase anchor protein 79 (AKAP79). This compound effectively inhibits the activation-induced sensitization by protein kinase A (PKA) or PKC of the transient receptor potential vanilloid 1 (TRPV1) at a concentration of 200 µM in isolated rat dorsal root ganglion (DRG) neurons. Additionally, it mitigates nocifensive behavior in mice elicited by formalin or phorbol 12-myristate 13-acetate (PMA014), enhances latency for paw withdrawal from radiant heat, and raises the mechanical threshold force required for paw withdrawal in a carrageenan-induced mouse model of inflammatory pain.

ω-Conotoxin CVIB is an antagonist of non-selective N- and P/Q-type voltage-gated calcium channels (VGCCs). It inhibits depolarization-activated whole-cell VGCC currents in dorsal root ganglion (DRG) neurons, exhibiting a pIC50 of 7.64 [1].

MRS 1523 can exert an antihyperalgesic effect through N-type Ca channel block and action potential inhibition in isolated rat dorsal root ganglion (DRG) neurons. MRS 1523 is an effective and selective adenosine A3 receptor antagonist Ki: 18.9 nM and 113 n

Veratridine is a benzoate-cevane found in Veratrum and Schoenocaulon. It activates sodium channels to stay open longer than normal.

Tat-CBD3A6K, a peptide derivative of the N-type voltage-gated calcium channel Cav2.2 and collapsin response mediator protein 2 (CRMP2) interaction inhibitor Tat-CBD3, has demonstrated efficacy in a rat model of antiretroviral neuropathic pain caused by stavudine (d4T). Administered at 10 mg/kg, it preserves paw withdrawal threshold, indicating pain relief, and reduces the number of action potentials in dorsal root ganglia (DRG) neurons from affected rats. Additionally, a 30 µM/animal dural dose of Tat-CBD3A6K lessens meningeal blood flow escalation triggered by capsaicin, showcasing its potential in managing neuropathic pain and inflammation.

Myr-Tat-CBD3 is a chemical compound that serves as an inhibitor of the protein-protein interaction between the N-type voltage-gated calcium channel Cav2.2 and collapsin response mediator protein 2 (CRMP2). This compound effectively disrupts the Cav2.2-CRMP2 interaction by about 81% at a 10 µM concentration and demonstrates an inhibitory concentration 50 (IC50) value of approximately 2.8 µM against potassium-induced calcium influx in primary rat dorsal root ganglion (DRG) neurons. Furthermore, at a concentration of 20 µM, Myr-Tat-CBD3 specifically inhibits calcium currents without affecting sodium currents in primary DRG neurons. Additionally, intrathecal administration of 20 µg/5 µl of Myr-Tat-CBD3 effectively mitigates carrageenan-induced declines in paw withdrawal latencies in rats, indicating its potential for pain relief. The compound also notably reduces cue-induced reinstatement of cocaine-seeking behavior in rats, suggesting therapeutic potential in addiction treatment.

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).