A low-trapping NMDA channel blocker
IC50: 4-7 μM
Lanicemine is a NMDA channel blocker.
NMDA receptors, glutamate-gated cation channels with high calcium permeability, play critical roles in various aspects of the biology. They are important for the development of the CNS, generation of rhythms, and the processes underlying memory, learning, and neuroplasticity.
In vitro: Previous study with lanicemine and ketamine found that both compounds could bind with low-to-moderate affinity to sites within the NMDA channel pore, exhibit strong voltage dependence, and have similar lack of NR2A vs NR2B subunit selectivity [1].
In vivo: In animal study, cortical EEG recordings were obtained from rats trained to perform an auditory detection task for food reward. Results showed that both lanicemine and ketamine produced pronounced dose-dependent elevations in spontaneous gamma-band EEG, but only gamma changes for ketamine were tightly coupled to increases in locomotor activity, indicating that lanicemine not only engaged brain circuits involved in the generation of gamma-EEG, but also influenced these networks independent of the broader systemslevel disruptions typical of ketamine [1].
Clinical trial: A qEEG crossover study was conducted in healthy volunteers but was stopped earlier than planned following two serious adverse events occurring during ketamine infusion. Significant increases in gamma-band EEG were found for both lanicemine and ketamine, and baseline-corrected gamma-EEG following lanicemine treatment was statistically indistinguishable from ketamine. Moreover, both lanicemine and ketamine produced significant reductions in prefrontal theta-cordance. Furthermore, no serious adverse events were observed associated with lanicemine [1].
Reference:
[1] G.? Sanacora, M. A. Smith, S. Pathak, et al. Lanicemine: A low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects. Molecular Psychiatry 19(9), 978-985 (2014).
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