L-687,414 is a glycine-site NMDA receptor antagonist or low-efficacy partial agonist (EmaxTooltip maximal efficacy ≈ 10%) which is used in scientific research. It is a close analogue of HA-966. The drug has been found to produce hyperlocomotion (a psychostimulant-like effect), analgesia or antinociceptive effects, anticonvulsant effects, and neuroprotective effects in animals. In contrast to uncompetitive NMDA receptor antagonists like ketamine and phencyclidine (PCP), L-687,414 has not been associated with the development of brain vacuoles (i.e., Olney's lesions) in animals. Trace amine-associated receptor 1 (TAAR1) partial and full agonists, including RO5166017, RO5203648, RO5256390, and RO5263397, have been found to reverse the hyperlocomotion induced by L-687,414 as well as by other NMDA receptor antagonists like PCP in rodents. Similarly, glycine transporter 1 (GlyT1) inhibitors reverse the hyperlocomotion induced by L-687,414 in rodents. As such, TAAR1 agonists and GlyT1 inhibitors may have antipsychotic-like properties.
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