The Novel Dipeptide Translocator Protein Ligand, Referred to As GD-23, Exerts Anxiolytic and Nootropic Activities.
The translocator protein (TSPO) promotes the translocation of cholesterol to the inner mitochondrial membrane and mediates steroid formation. In this study, we first report on a biological evaluation of the dipeptide GD-23 (N-carbobenzoxy-L tryptophanyl-L isoleucine amide), a structural analogue of Alpidem, the principal TSPO ligand. We show that GD-23 in a dose range of 0.05 to 0.5 mg/kg (i.p.) exhibits anxiolytic activity in the elevated plus maze test and nootropic activity in the object recognition test in scopolamine-induced amnesia in rodents. It was shown that GD-23 did not affect spontaneous locomotor activity, holding promise as a nonsedative anxiolytic agent. The anxiolytic and nootropic activities of GD-23 were abrogated by the TSPO specific ligand PK11195, which thus suggests a role for TSPO in mediating the pharmacological activity of GD-23.
V.V. Zakusov Research Institute of Pharmacology of RAMS, ul. Baltiyskaya, 8, Moscow, 125315, Russia.
P Yu
PY
Povarnina
V.V. Zakusov Research Institute of Pharmacology of RAMS, ul. Baltiyskaya, 8, Moscow, 125315, Russia.
S A
SA
Yarkov
V.V. Zakusov Research Institute of Pharmacology of RAMS, ul. Baltiyskaya, 8, Moscow, 125315, Russia.
T A
TA
Gudasheva
V.V. Zakusov Research Institute of Pharmacology of RAMS, ul. Baltiyskaya, 8, Moscow, 125315, Russia.
M A
MA
Yarkova
V.V. Zakusov Research Institute of Pharmacology of RAMS, ul. Baltiyskaya, 8, Moscow, 125315, Russia.
S B
SB
Seredenin
GD-23; anxiolytic activity; dipeptide; nootropic activity; translocator protein