Exploration of Drug Science

Table 4

Antidepressant-like activity of NGF, BDNF and NT-3 dipeptide mimetics in the forced swim test in mice

Parent neurotrophin	Code	Neurotrophin loop	Threshold dose (mg/kg, ip)	Activation of post-receptor signaling cascades			Decrease in immobility time compared to the control group (%)
Parent neurotrophin	Code	Neurotrophin loop	Threshold dose (mg/kg, ip)	PI3K/Akt	MAPK/ERK	PLC-γ1	Acute administration	Subchronic administration
NGF	GK-2 [67]	4	1.0	++	ns	++	ns	14
NGF	GK-6 [67]	1	2.0	+	+	+	ns	15
BDNF	GSB-106 [67]	4	1.0	+	++	++	20	16
	GSB-214 [67]	1	1.0	+	ns	++	ns	20
	GTS-201 [67]	2	Not active	ns	+	++	ns	ns
NT-3	GTS-301 [33]	4	10.0	ns	++	++	ns	27
NT-3	GTS-302 [36, 43]	4	0.5	++	++	+	31	34

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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 data on the reduction in immobility time compared to the control group (%) are presented as means. The reference drug Amitriptyline (10.0 mg/kg, ip) reduced immobility time under the same conditions in various experiments up to 40%