Ro 67-4853

Ro 67-4853 is a positive allosteric modulator of metabotropic glutamate 1 receptors (mGluR1), enhancing glutamate-induced calcium signaling through both the human and mouse mGlu1a receptors (pEC₅₀ = 7.16).^1,2 While only mildly potentiating mGluR5 signaling, this compound is without effect at mGluR2, mGluR4, or mGluR8, as well as at several other neural receptors.¹ Ro 67-4853 can also directly activate mGluR1 signaling in baby hamster kidney cells, leading to phosphorylation of ERK1/2 (EC₅₀ = 6.2 nM) and activation of adenylate cyclase (EC₅₀ = 11.7 μM).³ Ro 67-4853 can also be used to enhance neuronal stimulation in response to the mGluR1/mGluR5 agonist DHPG, both in vivo and in vitro (EC₅₀ = 95 nM).^1,4

WARNING This product is not for human or veterinary use.

1. Knoflach, F., Mutel, V., Jolidon, S., et al. Positive allosteric modulators of metabotropic glutamate 1 receptor: Characterization, mechanism of action, and binding site. Proc. Natl. Acad. Sci. USA 98(23), 13402-13407 (2001).

2. Hemstapat, K., de Paulis, T., Chen, Y., et al. A novel class of positive allosteric modulators of metabotropic glutamate receptor subtype 1 interact with a site distinct from that of negative allosteric modulators. Mol. Pharmacol. 70(2), 616-626 (2006).

3. Sheffler, D.J., and Conn, P.J. Allosteric potentiators of metabotropic glutamate receptor subtype 1a differentially modulate independent signaling pathways in baby hamster kidney cells. Neuropharmacology 55(4), 419-427 (2008).

4. Salt, T.E., Jones, H.E., Andolina, I.M., et al. Potentiation of sensory responses in ventrobasal thalamus in vivo via selective modulation of mGlu1 receptors with a positive allosteric modulator. Neuropharmacology 62(4), 1695-1699 (2012).