Ro 67-4853

Ro 67-4853 is a positive allosteric modulator (PAM) of mGluR1 (pEC₅₀=7.16 for rmGlu1a receptor). Ro67-4853 exhibits activity at all group I mGlu receptors including hmGlu1, rmGlu1, and rmGlu5. Ro 67-4853 enhances the potency of L-Glu by interacting with the transmembrane domain (TMD) of the receptor. Ro 67-4853 potentiates sensory synaptic responses to repetitive vibrissa stimulation^[1][2][3][4]. In Vitro: Ro67-4853 selectively potentiates responses to the agonist DHPG^[2].
Ro 67-4853 (1 µM) shifts the concentration-response curve (CRC) of glutamate approximately 2-fold, 15-fold, and 4.5-fold to the left respectively in BHK cells stably expressing mGluR1a^[4].
Ro 67-4853 (1 µM) activates p-ERK1/2 in the absence of agonist with a time course of activation peaking at 5 minutes in BHK cells^[4].
Ro 67-4853 (500 nM) potentiates glutamate-induced activation of mGluR1 as assessed by measures of cAMP production. Glutamate increases cAMP accumulation with an EC50 value of 32.08 µM in the absence of Ro 67-4853. The EC50 values for glutamate in the presence of Ro 67-4853 is 2.15 µM. Ro 67-4853 increases basal mGluR1-induced cAMP accumulation and potentiate glutamate-induced cAMP accumulation but have lower potencies at modulating the cAMP response than at regulating ERK1/2 phosphorylation or calcium mobilization^[4].