Ro 67-7476 is a positive allosteric modulator of mGlu1 receptors. Displays no activity at human mGlu1 receptors. Potentiates glutamate-induced calcium release with EC 50 of 60.1 nM.target: mGlu1 EC 50: 60.1 nM(1) Ro 67-7476 (10 μM) can directly block the GIRK channel (to 67 ± 2% of control). (2) Ro 67-7476 enhance the glutamate-induced current in all chimeric receptors containing the transmembrane (TM) region of rmGlu1a (R1, R1-R5N, R1-R5C, and R5-R1TM) but not in those containing the TM region of rmGlu5a (R5, R5-R1N, R5-R1C, and R1-R5TM.(3) The application of Ro 67-7476 (3 μM) produced no effect alone but resulted in a marked potentiation of the mGlu1 EPSC amplitude.
References:
[1]. Hemstapat K 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. 2006 Aug, 70(2), 616-26
[2]. Knoflach F et al. Positive allosteric modulators of metabotropic glutamate 1 receptor: characterization, mechanism of action, and binding site. Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13402-7.