AR-M 1896 is a novel, highly selective galanin type 2 receptor (GalR2) agonist (IC₅₀=1.76nM)[1-2]. AR-M 1896 modulates neuropeptide signaling pathways by specifically activating the GalR2 receptor, thereby exerting neuroprotective, anti-inflammatory, and pain-modulating effects. AR-M 1896 can be used in research related to acute myocardial infarction, neuropathic pain, and epilepsy[3-4].
In vitro, treatment of primary cultured cortical neurons ischemia model with AR-M 1896 (1nM to 10μM) for 15min did not increase neuronal viability or reduce lactate dehydrogenase (LDH) release in a dose-dependent manner, unlike galanin[5]. Treatment of rat pheochromocytoma (PC12) cells stably transfected with GFP-labeled galanin type 2 receptor (GalR2) with AR-M 1896 (100nM) for 24h induced caspase-dependent apoptosis, inhibited the PI3K/Akt signaling pathway, and caused cell cycle arrest in the sub‑G1 phase[6].
In vivo, AR-M 1896 (0.1μM/paw) was administered to rats via plantar injection on days 5 and 7 after median nerve chronic constriction injury (CCI). AR‑M 1896 slightly aggravated CCI-induced mechanical allodynia and significantly increased the number of c‑Fos‑positive neurons in the cuneate nucleus (CN) after electrical stimulation of the injured nerve[7]. AR‑M 1896 (3pmol) and calcitonin gene-related peptide (CGRP; 10pmol) were co-administered to CD-1 mice via intradermal injection; AR‑M 1896 significantly suppressed CGRP-induced inflammatory skin edema (plasma extravasation)[8].
References:
[1] Liu HX, Brumovsky P, Schmidt R, et al. Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord: selective actions via GalR1 and GalR2 receptors. Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9960-4.
[2] Serebryakova L, Pal'keeva M, Studneva I, et al. Galanin and its N-terminal fragments reduce acute myocardial infarction in rats. Peptides. 2019 Jan;111:127-131.
[3] Pirondi S, Fernandez M, Schmidt R, et al. The galanin-R2 agonist AR-M1896 reduces glutamate toxicity in primary neural hippocampal cells. J Neurochem. 2005 Nov;95(3):821-33.
[4] Kerekes N, Mennicken F, O'Donnell D, et al. Galanin increases membrane excitability and enhances Ca(2+) currents in adult, acutely dissociated dorsal root ganglion neurons. Eur J Neurosci. 2003 Dec;18(11):2957-66.
[5] Li Y, Mei Z, Liu S, et al. Galanin Protects from Caspase-8/12-initiated Neuronal Apoptosis in the Ischemic Mouse Brain via GalR1. Aging Dis. 2017 Feb 1;8(1):85-100.
[6] Tofighi R, Joseph B, Xia S, et al. Galanin decreases proliferation of PC12 cells and induces apoptosis via its subtype 2 receptor (GalR2). Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2717-22.
[7] Chen SH, Lue JH, Hsiao YJ, et al. Elevated galanin receptor type 2 primarily contributes to mechanical hypersensitivity after median nerve injury. PLoS One. 2018 Jun 21;13(6):e0199512.
[8] Schmidhuber SM, Rauch I, Kofler B, et al. Evidence that the modulatory effect of galanin on inflammatory edema formation is mediated by the galanin receptor 3 in the murine microvasculature. J Mol Neurosci. 2009 Feb;37(2):177-81.