Journal of Pharmaceutical and Biomedical Analysis, volume 223, pages 115125
LC-MS/MS determination of GTS-201, a dipeptide mimetic of the brain-derived neurotrophic factor, and neurotransmitter metabolites with application to a pharmacokinetic study in rats
Markin Pavel A
1
,
Lebedeva Svetlana A.
2
,
Kozin S.V.
2
,
Grigorevskikh E. M.
2
,
Kolik L.G.
3
,
Gudasheva Tatyana A
3
,
3
Publication type: Journal Article
Publication date: 2023-01-01
Quartile SCImago
Q2
Quartile WOS
Q2
Impact factor: 3.4
ISSN: 07317085, 1873264X
Drug Discovery
Spectroscopy
Pharmaceutical Science
Clinical Biochemistry
Analytical Chemistry
Abstract
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family with diverse psychopharmacological effects including antidepressant and anxiolytic actions. However, the clinical use of BDNF is limited due to its poor pharmacokinetic properties. The development of low-molecular-weight BDNF mimetics passing through the blood-brain barrier is an emerging strategy for improved managing psychiatric diseases. The present study characterizes a novel dipeptide mimetic of the 2nd BDNF loop named GTS-201, which exhibits psychotropic properties in experimental animal models of anxiety and alcohol dependence. The aim of this work was to study the pharmacokinetics of GTS-201 in rats at a saturating dosage of 5 mg/kg applied by the intraperitoneal route and to characterize the effects on neurotransmitter levels in the blood and brain. The maximum concentration (Cmax) of GTS-201 in the plasma (867 ± 69 ng/ml) was recorded at 35 ± 7.7 min after administration (Tmax) with a half-elimination period (T1/2) of 19.5 ± 1.8 min, while in the brain tissue Cmax was 14.92 ± 3.11 ng/ml, Tmax was 40.0 ± 7.7 min and T1/2 were 87.5 ± 12.7 min. The relative tissue availability of the GTS-201 for the brain reached 2.9%. At the dose applied, GTS-201 induced a significant increase of serotonin (5-fold) and dopamine levels in the brain tissue (8-fold) along with a decrease in cortisol content in blood plasma 45 min after acute administration. In summary, GTS-201 crosses the blood-brain barrier after acute administration and affects the activity of serotonergic and dopaminergic systems, which may underlie its neuropsychotropic effects described previously.
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Journal of Pharmaceutical and Biomedical Analysis
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Journal of Pharmaceutical and Biomedical Analysis
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Elsevier
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Elsevier
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Markin P. A. et al. LC-MS/MS determination of GTS-201, a dipeptide mimetic of the brain-derived neurotrophic factor, and neurotransmitter metabolites with application to a pharmacokinetic study in rats // Journal of Pharmaceutical and Biomedical Analysis. 2023. Vol. 223. p. 115125.
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Markin P. A., Lebedeva S. A., Kozin S., Grigorevskikh E. M., Kolik L., Gudasheva T. A., Appolonova S. A. LC-MS/MS determination of GTS-201, a dipeptide mimetic of the brain-derived neurotrophic factor, and neurotransmitter metabolites with application to a pharmacokinetic study in rats // Journal of Pharmaceutical and Biomedical Analysis. 2023. Vol. 223. p. 115125.
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TY - JOUR
DO - 10.1016/j.jpba.2022.115125
UR - https://doi.org/10.1016%2Fj.jpba.2022.115125
TI - LC-MS/MS determination of GTS-201, a dipeptide mimetic of the brain-derived neurotrophic factor, and neurotransmitter metabolites with application to a pharmacokinetic study in rats
T2 - Journal of Pharmaceutical and Biomedical Analysis
AU - Markin, Pavel A
AU - Lebedeva, Svetlana A.
AU - Kozin, S.V.
AU - Grigorevskikh, E. M.
AU - Kolik, L.G.
AU - Gudasheva, Tatyana A
AU - Appolonova, Svetlana A
PY - 2023
DA - 2023/01/01 00:00:00
PB - Elsevier
SP - 115125
VL - 223
SN - 0731-7085
SN - 1873-264X
ER -
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@article{2023_Markin,
author = {Pavel A Markin and Svetlana A. Lebedeva and S.V. Kozin and E. M. Grigorevskikh and L.G. Kolik and Tatyana A Gudasheva and Svetlana A Appolonova},
title = {LC-MS/MS determination of GTS-201, a dipeptide mimetic of the brain-derived neurotrophic factor, and neurotransmitter metabolites with application to a pharmacokinetic study in rats},
journal = {Journal of Pharmaceutical and Biomedical Analysis},
year = {2023},
volume = {223},
publisher = {Elsevier},
month = {jan},
url = {https://doi.org/10.1016%2Fj.jpba.2022.115125},
pages = {115125},
doi = {10.1016/j.jpba.2022.115125}
}