Preclinical Pharmacokinetic and Pharmacodynamic Studies of Pharmaceutical Compositions of the Dipeptide Anxiolytic GB-115
- Authors: Zherdev V.P.1, Boiko S.S.1, Konstantinopol’skii M.A.1, Raskin S.Y.1, Alekseev K.V.1, Gudasheva T.A.1, Mart’yanov V.A.1, Kolik L.G.1
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Affiliations:
- Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
- Issue: Vol 50, No 5 (2016)
- Pages: 323-327
- Section: Drugs
- URL: https://journals.rcsi.science/0091-150X/article/view/244385
- DOI: https://doi.org/10.1007/s11094-016-1445-7
- ID: 244385
Cite item
Abstract
Four pharmaceutical compositions for oral use that contained the dipeptide anxiolytic GB-115 as the active ingredient underwent preclinical trials in male laboratory white rats. Various excipients added to the compositions and their preparation technologies had significant effects on the dipeptide pharmacokinetics. It was shown that compositions 2 and 4 had advantages according to the main pharmacokinetic characteristics reflecting the bioavailability of GB-115. The pharmacological activities of GB-115 compositions 1 – 4 at oral doses of 0.3 – 0.9 mg/kg were studied in an elevated plus-maze (EPM) test. It was established that composition 4, which included micronized substance and a hydrophilic matrix with controlled release of the active ingredient (hydroxypropylmethylcellulose), possessed the highest anxiolytic activity and increased the residence time in the EPM open arms at doses of 0.3 mg/kg (p < 0.01) and 0.9 mg/kg (p < 0.01) as compared with the placebo group. Pharmaceutical composition 4 could be recommended for creating a controlled-release solid dosage form based on the comprehensive studies.
About the authors
V. P. Zherdev
Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Author for correspondence.
Email: zherdevpharm@mail.ru
Russian Federation, 8 Baltiiskaya St., Moscow, 125315
S. S. Boiko
Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: zherdevpharm@mail.ru
Russian Federation, 8 Baltiiskaya St., Moscow, 125315
M. A. Konstantinopol’skii
Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: zherdevpharm@mail.ru
Russian Federation, 8 Baltiiskaya St., Moscow, 125315
S. Yu. Raskin
Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: zherdevpharm@mail.ru
Russian Federation, 8 Baltiiskaya St., Moscow, 125315
K. V. Alekseev
Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: zherdevpharm@mail.ru
Russian Federation, 8 Baltiiskaya St., Moscow, 125315
T. A. Gudasheva
Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: zherdevpharm@mail.ru
Russian Federation, 8 Baltiiskaya St., Moscow, 125315
V. A. Mart’yanov
Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: zherdevpharm@mail.ru
Russian Federation, 8 Baltiiskaya St., Moscow, 125315
L. G. Kolik
Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: zherdevpharm@mail.ru
Russian Federation, 8 Baltiiskaya St., Moscow, 125315