intrathecal

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.

K 41498 is a selective peptide antagonist targeting both corticotropin-releasing factor receptor 2α (CRF2α) and CRF2β, demonstrating high affinity with Kis of 0.66 and 0.62 nM, respectively, in HEK293 cells expressing these human receptors. Its selectivity is evident as it exhibits a significantly reduced affinity for CRF1 receptor (Ki = 425 nM in HEK293 cells expressing the human CRF1 receptor). Additionally, K 41498, when administered intravenously at 1.84 µg/animal, effectively mitigates urocortin-induced hypotension in rats. Furthermore, its intrathecal delivery ranging from 0.075 to 0.5 µmol/animal significantly lowers the mechanical paw withdrawal threshold in a rat model, indicating its potential utility in managing nociception triggered by complete Freund's adjuvant.

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.

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.