It was found that GK-2 at a daily dose of 1 mg/kg, intraperitoneally, during 7 days statistically significantly reduces brain infarct volume by 20-60% at the first injection from 4 to 24h, with the highest effect 6-8 hours after surgery. Thus, the 'therapeutic window' of GK-2 detected in the experiment is no less than 24 hours, which exceeds the existing neuroprotective agents.
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.
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