The effects of dipeptide mimetics of NGF, BDNF, and NT-3 on pain sensitivity in the tail flick and hot plate tests in mice and rats

Parent neurotrophinCodeNeurotrophin loopThreshold dose, (mg/kg, ip)Activation of post-receptor signaling cascadesPain threshold compared to the control group 24 h after administration of the compound (%)
PI3K/AktMAPK/ERKPLC-γ1
NGFGK-2 [37]41.0++ns++144
(analgesia)
GK-6 [37]12.0+++62
(algesia)
BDNFGSB-106 [98]40.1+++++144
(analgesia)
GSB-2141Not active+ns++ns
NT-3GTS-301 [99]40.01ns++++120
(analgesia)
GTS-3020.1+++++110
(analgesia)

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-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. Effects of mimetics on pain thresholds are presented as average values. Morphine, used as a reference drug, increased pain thresholds by 200% in the same experimental setup, and this effect persisted for 1 h after its administration