New L- valine peptide mimetics as potential neuropharmacological agents

作者：Tancheva L P; Encheva E N^*; Tsekova D S; Alova L G; Stancheva S L; Petkov V V; Novoselski M T; Klisurov R

来源：Bulgarian Chemical Communications, 2012, 44(3): 262-266.

• peptide mimetics
• L-valine
• nicotinic acid derivatives
• cognitive functions
• neuromediators
• neuropharmacological effect

Aim of the present study was to evaluate the effect of four recently synthesized peptide mimetics, derivatives of L- Valine, containing moieties of nicotinic/isonicotinic acids and hydrophobic spacers with two different lengths, on the cognitive functions of rodents. Male Albino mice were treated with these compounds in daily doses 125 and 250 mg/kg b. wt. for 3 consecutive days. Their learning and memory were evaluated with Step-through test, their exploratory activity with Hole-board test and their muscular coordination - with Rota-rod test. The ability of the used substances to affect metabolism of biogenic amines in hippocampus was studied in Wistar rats, 1 hour after single treatment (250 mg/kg i.p.). Our results revealed a significant dose-dependent effect of two of the compounds, which appear as positional isomers and contain longer hydrophobic spacer. Their effect on the parameters of learning and memory, exploratory activity and muscular coordination, was well pronounced. The levels of neuromediators in hippocampus were significantly changed after a single treatment. Serotonin (5-HT) levels were increased significantly by both compounds, one of which increased also noradrenaline levels. The improving effect on cognitive functions of rodents is most probably related to the presence of L-Valine, as well as nicotinic or isonicotinic residue. The much stronger influence of the pair with a longer hydrophobic spacer is due to the better lipid solubility and the possible blood-brain barrier transport related to it, so as to modulate biogenic neuromediators%26apos; levels in rat hippocampus.

• 出版日期2012
• 单位北京化工大学