L-701324 appears to be an antagonist of the NMDA receptor and acts at the glycine binding site.[2] This means that it prevents the receptor from activating by blocking the binding of glycine, a required co-agonist in addition to glutamate.
Potential use as an antidepressant
L-701324 exhibited antidepressant behavior in mice by reducing depression-like behavior caused by the forced swimming test, the tail suspension test, and the chronic unpredictable mild stress model.[3]
In another animal study, a combination of an adenosine receptor antagonist, such as caffeine, with an NMDA receptor antagonist, such as L-701324, showed a synergistic effect that might have use as an antidepressant.[4]
^Priestley T, Laughton P, Macaulay AJ, Hill RG, Kemp JA (1996). "Electrophysiological characterisation of the antagonist properties of two novel NMDA receptor glycine site antagonists, L-695,902 and L-701,324". Neuropharmacology. 35 (11): 1573–1581. doi:10.1016/s0028-3908(96)00141-4. PMID9025105.
^Liu L, Ji CH, Wang Y, Zhao J, Liu Y, Tang WQ, et al. (February 2021). "Antidepressant-like activity of L-701324 in mice: A behavioral and neurobiological characterization". Behavioural Brain Research. 399: 113038. doi:10.1016/j.bbr.2020.113038. PMID33276033.
