N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor that is expressed throughout the central nervous system where it has been found to have a key role in regulating glutamatergic signaling that controls signaling and plasticity at excitatory synapses[3]. Rapastinel is an NMDAR modulator that has characteristics of a glycine site partial agonist. It is a robust cognitive enhancer and facilitates hippocampal long-term potentiation (LTP) of synaptic transmission in slices. Rapastinel produced an antidepressant like effect in the USVs (ultrasonic vocalization) test, as indexed by an increase in hedonic 50-kHz USVs [F(1, 20) = 12.4, P < 0.05] and a decrease in aversive 20-kHz USVs [F(1, 20) = 6.8, P < 0.05]. Rapastinel also produced an anxiolytic effect in the open field, as indexed by increased center time [F(1, 20) = 19.2, P < 0.05] without altering locomotor activity as measured by line crosses [F(1, 20) = 0.0, P > 0.05]. Further, A single dose of rapastinel (3 mg/kg IV) facilitated learning and memory in multiple models 1 day to 1 week post-dosing. A single in vivo dose of rapastinel (3 mg/kg IV) in 2–3 month old male SD rats significantly enhanced the magnitude of long-term potentiation (LTP) of synaptic transmission compared to vehicle treated controls. In male 2–3 month old rats, rapastinel (3 mg/kg IV) significantly induced increases in mature spines in distal dendrites of the dentate gyrus and Layer 5 of the MPFC 24 hrs post-dosing[4].
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