电邮这篇文章 Synthesis and Cerebrovascular Anti-Ischemic Activity of New 5-Hydroxyadamantan-2-One Derivatives
- 作者: Kurza E.V.1, Avdyunina N.I.1, Gan’shina T.S.1, Maslennikov D.V.1, Turilova A.I.1, Pyatin B.M.1, Grushevskaya L.N.1, Zaitseva N.M.1, Bol’shakova R.F.1, Kovalev G.I.1, Vasil’eva E.V.1, Mirzoyan R.S.1
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隶属关系:
- V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
- 期: 卷 52, 编号 2 (2018)
- 页面: 103-107
- 栏目: Search for New Drugs
- URL: https://journal-vniispk.ru/0091-150X/article/view/245013
- DOI: https://doi.org/10.1007/s11094-018-1772-y
- ID: 245013
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详细
New 5-hydroxyadamantan-2-one derivatives with heteroaromatic, aromatic, and aliphatic acids (nicotinic, succinic, p-chlorophenoxyacetic, 3,4,5-trimethoxybenzoic, and anisic) were synthesized. Their pharmacological properties were studied to discover compounds with cerebrovascular anti-ischemic activity and without hypotensive activity. Esters of succinic acid and 5-hydroxyadamantan-2-one (diester Ia and monoester Ib, 100 mg/kg, i.v.) exhibited the most potent effect on cerebral circulation under ischemic conditions. They did not lower arterial blood pressure. The monoester was less toxic with LD50 740.0 (676.0 – 804.0) mg/kg. Analysis of the cerebrovascular effects of the succinate esters of 5-hydroxyadamantan-2-one using bicuculline revealed a GABA-ergic mechanism of action on cerebral vessels. However, radioligand analysis in vitro using the specific ligand [3H]-SR 95531 found that these esters did not compete for rat-brain membrane GABAA-receptors. Thus, the monoester of succinic acid and 5-hydroxyadamantan-2-one possessed pronounced cerebrovascular anti-ischemic activity and did not produce hypotensive effects. The latter circumstance differentiated it from well-known drugs used in neurology (picamilon, Mexidol, nimodipine, cinnarizine, and Cavinton).
作者简介
E. Kurza
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
N. Avdyunina
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
T. Gan’shina
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
D. Maslennikov
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
A. Turilova
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
B. Pyatin
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
L. Grushevskaya
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
N. Zaitseva
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
R. Bol’shakova
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
G. Kovalev
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
E. Vasil’eva
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
R. Mirzoyan
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: chem@folium.ru
俄罗斯联邦, 8 Baltiiskaya St., Moscow, 125315
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