Memory-enhancing activity of dipeptide mimetics of BDNF and NT-3 in the novel object recognition test in rats
| Parent neurotrophin | Code | Neurotrophin loop | Threshold dose (mg/kg, ip) | Activation of post-receptor signaling cascades | Memory-enhancing activity | ||
|---|---|---|---|---|---|---|---|
| PI3K/Akt | MAPK/ERK | PLC-γ1 | |||||
| NGF | GK-2 [79] | 4 | 0.5 | ++ | ns | ++ | Improves long-term memory |
| GK-6 [79] | 1 | Not active | + | + | + | ns | |
| BDNF | GSB-106 [79] | 4 | Not active | + | ++ | ++ | ns |
| GSB-214 [79] | 1 | 0.1 | + | ns | ++ | Improves long-term memory | |
| GTS-201 [79] | 2 | Not active | ns | + | ++ | ns | |
| NT-3 | GTS-301 | 4 | 1.0 | ns | ++ | ++ | 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