Differences Between Cerebrovascular and Anti-Ischemic Effects of Dopamine, Docosahexaenoyldopamine, and GABA–Docosahexaenoyldopamine Conjugate
- Authors: Mirzoyan R.S.1, Gan’shina T.S.1, Topchyan A.V.1, Khailov N.A.1, Kurdyumov I.N.1, Kovalev G.I.1, Zimin I.A.1, Firstova Y.Y.1, Vasil’eva E.V.1, Gretskaya N.M.2, Bezuglov V.V.2
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Affiliations:
- Zakusov Institute of Pharmacology
- Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
- Issue: Vol 49, No 10 (2016)
- Pages: 661-666
- Section: Article
- URL: https://journals.rcsi.science/0091-150X/article/view/244269
- DOI: https://doi.org/10.1007/s11094-016-1348-7
- ID: 244269
Cite item
Abstract
The cerebrovascular and anti-ischemic effects of dopamine and synthetic docosahexaenoyldopamine (DHA-DA) and the GABA–DHA-DA conjugate (OXL1220) were compared and found to differ. Dopamine and DHA-DA increased blood flow in intact and ischemic brain that was associated with pronounced hypertensive reactions. The latter inhibited dopamine transporter with IC50 = 29 μM but was practically inactive as a ligand for dopamine receptors. OXL1220 produced a selective vasodilating effect on blood flow in brain subjected to transient global ischemia. Only OXL1220 competed in vitro for specific binding sites of [3H]-gabazine in rat-brain GABAA-receptors. Therefore, conjugation of a neuromediator (GABA) to the DHA-DA changed the dopaminergic activity of the compound to GABA-ergic with respect to vascular tone in ischemic brain.
About the authors
R. S. Mirzoyan
Zakusov Institute of Pharmacology
Email: chem@folium.ru
Russian Federation, Baltiiskaya Ul. 8, Moscow, 125315
T. S. Gan’shina
Zakusov Institute of Pharmacology
Email: chem@folium.ru
Russian Federation, Baltiiskaya Ul. 8, Moscow, 125315
A. V. Topchyan
Zakusov Institute of Pharmacology
Email: chem@folium.ru
Russian Federation, Baltiiskaya Ul. 8, Moscow, 125315
N. A. Khailov
Zakusov Institute of Pharmacology
Email: chem@folium.ru
Russian Federation, Baltiiskaya Ul. 8, Moscow, 125315
I. N. Kurdyumov
Zakusov Institute of Pharmacology
Email: chem@folium.ru
Russian Federation, Baltiiskaya Ul. 8, Moscow, 125315
G. I. Kovalev
Zakusov Institute of Pharmacology
Email: chem@folium.ru
Russian Federation, Baltiiskaya Ul. 8, Moscow, 125315
I. A. Zimin
Zakusov Institute of Pharmacology
Email: chem@folium.ru
Russian Federation, Baltiiskaya Ul. 8, Moscow, 125315
Yu. Yu. Firstova
Zakusov Institute of Pharmacology
Email: chem@folium.ru
Russian Federation, Baltiiskaya Ul. 8, Moscow, 125315
E. V. Vasil’eva
Zakusov Institute of Pharmacology
Email: chem@folium.ru
Russian Federation, Baltiiskaya Ul. 8, Moscow, 125315
N. M. Gretskaya
Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: chem@folium.ru
Russian Federation, Ul. Miklukho-Maklaya 16/10, Moscow, 117997
V. V. Bezuglov
Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: chem@folium.ru
Russian Federation, Ul. Miklukho-Maklaya 16/10, Moscow, 117997