Glutamate, the major excitatory neurotransmitter in the CNS, activates eight known subtypes of metabotropic glutamate receptors (mGluRs). Highly selective modulators designed to act at allosteric sites on certain mGluR subtypes are being developed to preferentially regulate subtype-specific, glutamate-induced receptor activation. Ro 01-6128 is a positive allosteric modulator of mGluR1 that can potentiate glutamate-induced calcium release at rat mGluR1a with an EC50 value of 104 nM. Ro 01-6128 activates ERK1/2 phosphorylation in the absence of exogenously added glutamate with an EC50 value of 248 nM and potentiates glutamate-induced cAMP production with an EC50 value of 21.5 μM.
