nocifensive

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)

PF-4840154 is a potent, selective agonist of the rat and human TrpA1 channel, eliciting TrpA1-mediated nocifensive behavior in mouse, with EC50 values of 97 nM and 23 nM for [rTrpA1] and [hTrpA1], respectively.

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.