TABLE 4

Biochemical effects implicating glutamatergic neurotransmission

Studies and experiments that did not identify an effect are not summarized in this table; please refer to the text for these details.

CompoundConcentration/DoseTimingEffectSystemReferences
BDNF
  (2R,6R)-HNK10 mg/kg, i.p.24 h post-treatmentIncreased BDNF protein levelsMouse hippocampusZanos et al. (2016)
10 mg/kg, i.p.30 min post-treatmentIncreased BDNF protein levelsMouse hippocampusLumsden et al. (2019)
10 and 50 nM1-h exposureIncreased BDNF releaseRat primary neuronsFukumoto et al. (2019)
10–100 µM15-min exposureDecreased TrkB/AP-2 interactionsMG87:TRKB cellsFred et al. (2019)
  (2S,6S)-HNK10 mg/kg, i.p.30–60 min post-treatmentIncreased extracellular BDNF levelsMouse prefrontal cortexAnderzhanova et al. (2020)
cAMP
  (2R,6R)-HNK10 µM15-min exposureIncreased cAMP accumulationC6 cellsWray et al. (2019)
eEF2
  (2R,6R)-HNK10 mg/kg, i.p.1 h post-treatmentDecreased eEF2 phosphorylationMouse hippocampusZanos et al. (2016)
24 h post-treatment
50 µM30-min exposureDecreased eEF2 phosphorylationMouse primary neuronsSuzuki et al. (2017)
mTOR and downstream pathways
  (2R,6R)-HNK10 mg/kg, i.p.30 min post-treatmentIncreased p-mTORMouse hippocampusLumsden et al. (2019)
30 mg/kg, i.p.30 min post-treatmentIncreased p-mTORMouse prefrontal cortexFukumoto et al. (2019)
1–50 nM1-h exposureIncreased pERKRat primary neuronsFukumoto et al. (2019)
  (2S,6S)-HNK20 mg/kg, i.v.20 min post-treatmentIncreased p-mTORRat prefrontal cortexPaul et al. (2014)
0.01–1 nM1-h exposurePC-12 cells
20 mg/kg, i.v.20–60 min post-treatmentIncreased p4E-BP1Rat prefrontal cortexPaul et al. (2014)
Increased pp70S6K
0.5 nM1-h exposureIncreased p4E-BP1PC-12 cellsPaul et al. (2014)
0.5–1 nM1-h exposureIncreased pERK
0.1–1 nM1-h exposureIncreased pAkt

  • pAkt, phosphorylated protein kinase B; p-MTOR, phosphorylated mTOR; pp70S6K, phosphorylated p70S6 kinase; p4E-BP1, phosphorylated eukaryotic initiation factor 4E-binding protein 1.