CNS-5161

CNS-5161 is a selective, non-competitive NMDA receptor antagonist that primarily targets the GluN2B subunit. CNS-5161 inhibits NMDA receptor-mediated excitatory neurotransmission in both in vitro and in vivo experiments, thereby facilitating the study of neuroprotective mechanisms and related signaling pathways. CNS-5161 is commonly used in neuroscience research to assess excitotoxicity and neuronal survival in model systems, and can be employed in studies of the mechanisms underlying central nervous system disorders.

Method: [³H]CNS-5161 (0.1–2.5 nM) was incubated with brain cell membranes. Control groups (± glutamate/glycine) were established, and 100 μM MK-801 was used to assess non-specific binding. Kd and Bmax were determined using Scatchard analysis.
Results: [³H] CNS-5161 exhibits monovalent, high-affinity binding; at 37°C, Kd = 3.1 nM and Bmax = 3.2 pmol/mg protein. [2]

Methods: Rats were administered 1 mCi/kg of [³H] CNS-5161 via the tail vein, pretreated with saline, NMDA, MK-801, or NMDA+MK-801. Tissues were harvested at 5–120 min to measure radioactivity, and the brain region/cerebellum ratio was calculated.
Results: The drug rapidly entered the brain, with brain uptake reaching 1.46% ID at 5 min; brain distribution in normal rats: hippocampus and cortex > thalamus > striatum > cerebellum, with a cortex/cerebellum ratio of 1.4; NMDA pretreatment increased the hippocampus/cerebellum ratio to 1.6–1.9, and MK-801 blocked this increase. [2]