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 within the receptor are being developed to preferentially target individual mGluR subtypes in order to determine their distinct pharmacological roles. ML-298 is a negative allosteric modulator of mGlu3 (IC50 = 0.66 μM) that displays 15-fold selectivity over mGlu2 and inactivity against mGlu5.
