AZ 12216052

AZ 12216052 is a mGluR8 positive allosteric modulator, and helps mGluR8 modulate signaling inputing to retinal ganglion cells. AZ 12216052 exhibits antianxiety effect[1][2][3][4].

Signaling Pathways >> GPCR/G Protein >> mGluR

Research Areas >> Neurological Disease

mGlu8

mGluR8 may modulates the synaptic inputs to retinal ganglion cells[1]. AZ 12216052 (10 μM) enhances the peak excitatory currents of ON-, OFF- currents in ON-OFF-ganglion cells, with a dependent way on the intensity of the light stimuli[1]. AZ 12216052 shows impact of cell differentiation and (0.01-1 μM; 24-48 h) reduces Dox-induced human neuroblastoma SH-SY5Y cell damage partially[2]. AZ 12216052 stimulates proliferation and attenuates staurosporine (St)- and doxorubicin (Dox)-induced toxicity in UN-SH-SY5Y cells[2]. AZ12216052 (10 μM) enhances glutamate activity of human mGluR8b receptor expressed in GHEK cells[3]. Cell Viability Assay[2] Cell Line: UN- and RA-SH-SY5Y cells Concentration: 0.01-1 μM Incubation Time: 48 hours Result: Increased cell viability at 0.1 μM, and protected undifferentiated neuroblastoma cells against damaging effects of Iri or Cis.

AZ 12216052 (10 mg/kg; i.p.; 2 h prior to testing) reduces measures of anxiety, without affecting the velocity of the mice[3]. AZ12216052 (10 mg/kg; i.p.; single dose) exhibits remaining anxiolytic effects, might involve mGluR4 in mGluR8−/− mice, as the mGluR4 PAM (Positive Allosteric Modulator) VU 0155041 also reduces measures of anxiety in wild-type mice[4]. Animal Model: WT and Apolipoprotein E-deficient (Apoe−/−) mice (C57BL/6J, 2-month-old) in the elevated zero maze[3] Dosage: 10 mg/kg Administration: Intraperitoneal injection; singel dose, 2 h prior to testing Result: Reduced measures of anxiety in the elevated zero maze without affecting the velocity of the mice. Reduced the acoustic startle response.

[1]. Reed BT, et al. Differential modulation of retinal ganglion cell light responses by orthosteric and allosteric metabotropic glutamate receptor 8 compounds. Neuropharmacology. 2013 Apr;67:88-94.

[2]. Jantas D, et al. Allosteric and Orthosteric Activators of mGluR8 Differentially Affect the Chemotherapeutic-Induced Human Neuroblastoma SH-SY5Y Cell Damage: The Impact of Cell Differentiation State. Basic Clin Pharmacol Toxicol. 2018 Oct;123(4):443-451.

[3]. Duvoisin RM, et al. Acute pharmacological modulation of mGluR8 reduces measures of anxiety. Behav Brain Res. 2010 Oct 15;212(2):168-73.

[4]. Duvoisin RM, et al. Opposing roles of mGluR8 in measures of anxiety involving non-social and social challenges. Behav Brain Res. 2011 Aug 1;221(1):50-4.