17 March 2025
Glutamate is a vital central nervous system neurotransmitter that plays a role in various neuronal functions. The metabotropic glutamate receptors (mGluRs) regulate glutamate release and signaling pathways. Among these receptors, mGluR2, a receptor highly expressed in limbic regions throughout the brain, functions as an auto-receptor at pre-synaptic terminals. It plays a crucial role in controlling synaptic glutamate release, effectively reducing glutamate release and restoring balance to overactive circuits within the cortico-limbic system.
Studies have shown that activating mGluR2 receptors at amygdala synapses induces specific synaptic changes in vitro. This activation has been found to promote anxiolytic-like behavior in rodents in vivo and alleviate symptoms of generalized anxiety disorder in human trials. These findings suggest that targeting mGluR2 receptors may be effective in modulating threat response behavior.
To accelerate your research on excitatory neurotransmission in over-activated circuits, we offer BI-4737, a specific positive allosteric mGluR2 modulator free of charge via opnMe. It comes along with the structurally similar, but inactive analogue BI-4576 as a negative control. Researchers can use them to investigate the roles of mGluR2 in vitro and in vivo. Interested researchers will receive the molecule for free and have full ownership of their results. We encourage researchers to publish their findings as part of our commitment to open science.
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About BI-4737:
BI-4737 is a positive allosteric modulator (PAM) of the metabotropic glutamate receptor 2 (mGluR2). Mechanistically, it represents a neuronal GPCR that is negatively coupled to adenylyl cyclase. BI-4737 exhibits an in vitro potency in the single-digit nanomolar range on rat mGluR2 and in the double-digit nanomolar range on human mGluR2. It has a medium predicted clearance and a high Caco-2 efflux ratio. BI-4737 shows good exposure in vivo when administered orally at a dose of 25 mg/kg and intraperitoneally at a dose of 50 mg/kg.
About opnMe:
opnMe.com, the open innovation portal of Boehringer Ingelheim, fosters science and collaboration initiatives in areas of high unmet medical need. As part of our first pillar, the “Molecules to Order”, we share well-characterized tool compounds free of charge with no IP strings attached. These are complemented by “Molecules for Collaboration” where we offer access to unprecedented, often unpublished molecules, together with an attractive funding package. Interested scientists are invited to submit testable research hypotheses with these assets in novel diseases or combinations. With our “opn2EXPERTS” and “techMATCH” programs, we enlist scientific advice on key biologic issues to fuel further drug discovery and deliver novel solutions that benefit unmet patient needs. Our opn2TALENTS PostDoc grants, provide an opportunity for high-caliber talents to pitch their scientific approaches for well-defined research questions to conduct their research at one of our discovery research sites.