CPCCOEt is a non-competitive metabotropic glutamate receptor 1 (mGluR1) antagonist. CPCCOEt inhibits receptor signaling by binding to the transmembrane domain of mGluR1, disrupting the intramolecular interaction between the agonist-bound extracellular domain and the transmembrane domain. CPCCOEt can be used in neuroscience and oncology-related research[1-4].
In vitro, Hs683, A172, and U87 glioma cell lines were treated with CPCCOEt (100-350μM) for five days. CPCCOEt significantly reduced the viability of these cells in a concentration-dependent manner[5]. CHO cells expressing the human mGlu1a receptor were pretreated with CPCCOEt (3μM–300μM) for 30 minutes, followed by stimulation with L-quisqualate (10μM) for 30 minutes. CPCCOEt significantly inhibited L-quisqualate-induced phosphoinositide hydrolysis and reduced mGlu1a receptor-mediated signaling[6].
In vivo, CPCCOEt (500nmoles; single treatment) was administered via intrathecal injection to chronic constriction injury rats 20 minutes before formalin stimulation. CPCCOEt significantly reduced formalin-induced nociception in CCI rats, as well as the associated increases in spinal glutamate concentrations[7]. In male C57BL/6J mice (10-24 weeks old), CPCCOEt (10 and 30mg/kg; single treatment) was administered via intraperitoneal injection 10 minutes before ethanol (4.0g/kg) administration. CPCCOEt did not significantly alter ethanol-induced sedation and hypnotic effects[8].
References:
[1] Litschig S, Gasparini F, Rueegg D, et al. CPCCOEt, a noncompetitive metabotropic glutamate receptor 1 antagonist, inhibits receptor signaling without affecting glutamate binding. Mol Pharmacol. 1999 Mar;55(3):453-61.
[2] Bräuner-Osborne H, Jensen AA, Krogsgaard-Larsen P. Interaction of CPCCOEt with a chimeric mGlu1b and calcium sensing receptor. Neuroreport. 1999 Dec 16;10(18):3923-5.
[3] Fukunaga I, Yeo CH, Batchelor AM. The mGlu1 antagonist CPCCOEt enhances the climbing fibre response in Purkinje neurones independently of glutamate receptors. Neuropharmacology. 2007 Feb;52(2):450-8.
[4] Haas HS, Pfragner R, Siegl V, et al. The non-competitive metabotropic glutamate receptor-1 antagonist CPCCOEt inhibits the in vitro growth of human melanoma. Oncol Rep. 2007 Jun;17(6):1399-404.
[5] Dalley CB, Wroblewska B, Wolfe BB, et al. The Role of Metabotropic Glutamate Receptor 1 Dependent Signaling in Glioma Viability. J Pharmacol Exp Ther. 2018 Oct;367(1):59-70.
[6] Hermans E, Nahorski SR, Challiss RA. Reversible and non-competitive antagonist profile of CPCCOEt at the human type 1alpha metabotropic glutamate receptor. Neuropharmacology. 1998 Dec;37(12):1645-7.
[7] Kumar N, Laferriere A, Yu JS, et al. Metabotropic glutamate receptors (mGluRs) regulate noxious stimulus-induced glutamate release in the spinal cord dorsal horn of rats with neuropathic and inflammatory pain. J Neurochem. 2010 Jul;114(1):281-90.
[8] Sharko AC, Hodge CW. Differential modulation of ethanol-induced sedation and hypnosis by metabotropic glutamate receptor antagonists in C57BL/6J mice. Alcohol Clin Exp Res. 2008 Jan;32(1):67-76.