Kinetics of Semax Penetration into the Brain and Blood of Rats after Its Intranasal Administration

K. V. Shevchenko,# I. Yu. Nagaev, L. Yu. Alfeeva, L. A. Andreeva, A. A. Kamenskii, N. G. Levitskaya, V. P. Shevchenko, I. A. Grivennikova, and N. F. Myasoedov

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Institute of Molecular Genetics, Russian Academy of Sciences, pl. akademika Kurchatova 2, Moscow, 123182 Russia

The radioactive peptide analogue Semax, corresponding to the ACTH(4-10) sequence (Met-Glu-His-Phe-Pro-Gly-Pro), with a molar radioactivity of 56 Ci/mmol labeled with tritium at the C-terminal Pro was prepared. The labeled peptide was used for studying the kinetics of Semax penetration into rat brain and blood after its intranasal administration (50 μg/kg, 20 μl of solution) to nonbred white rats of body mass 200-250 g. It was demonstrated that 0.093% of the total introduced radioactivity per gram can be found in the rat brain 2 min after the administration; 80% of this radioactivity belonged to Semax, and the rest, to its metabolites. The peptide undergoes rapid enzymatic degradation, with the tripeptide Pro-Gly-Pro prevailing in biological samples relative to the total content of Semax and its metabolites.

Key words: brain, blood, metabolism, pharmacokinetics, rats, Semax , tritium

Russian Journal of Bioorganic Chemistry 2006, 32 (1):57-62