Memory-enhancing activity of dipeptide mimetics of BDNF and NT-3 in the novel object recognition test in rats

Parent neurotrophinCodeNeurotrophin loopThreshold dose (mg/kg, ip)Activation of post-receptor signaling cascadesMemory-enhancing activity
PI3K/AktMAPK/ERKPLC-γ1
NGFGK-2 [79]40.5++ns++Improves long-term memory
GK-6 [79]1Not active+++ns
BDNFGSB-106 [79]4Not active+++++ns
GSB-214 [79]10.1+ns++Improves long-term memory
GTS-201 [79]2Not activens+++ns
NT-3GTS-30141.0ns++++Improves short- and long-term memory
GTS-302 [43]1.0+++++Improves short- and long-term memory

ip: intraperitoneally; NGF: nerve growth factor; BDNF: brain-derived neurotrophic factor; NT-3: neurotrophin-3; MAPK/ERK: mitogen-activated protein kinase/extracellular signal-regulated kinase; PLC-γ1: phospholipase C-gamma; GK-2: bis-(monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide; GK-6: bis-(N-aminocaproyl-glycyl-L-lysine) hexamethylenediamide; GSB-106: bis-(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide; GSB-214: bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylenediamide; GTS-201: bis-(N-hexanoyl-L-seryl-L-lysine) hexamethylenediamide; GTS-301: bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) hexamethylenediamide; GTS-302: bis-(N-gamma-oxybutyryl-L-glutamyl-L-asparagine) hexamethylenediamide; +: the effect is inferior to the full-length neurotrophin in terms of intensity and/or duration; ++: the effect is comparable to the full-length neurotrophin in terms of intensity and duration; ns: non-significant. All effects not labeled as “ns” are statistically significant. The reference drug Piracetam (200.0 mg/kg, ip), under the same conditions, improved only short-term memory