Synthesis and Pharmacological Properties of Adamantane-Containing Bis-Cationic Compounds
- Авторы: Gmiro V.E.1, Serdyuk S.E.1, Veselkina O.S.2
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Учреждения:
- Institute of Experimental Medicine
- Vertex Pharmaceutical Company
- Выпуск: Том 52, № 10 (2019)
- Страницы: 830-834
- Раздел: Article
- URL: https://ogarev-online.ru/0091-150X/article/view/245493
- DOI: https://doi.org/10.1007/s11094-019-1909-7
- ID: 245493
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Аннотация
The bis-cationic compound 1-amino-4-(1-adamantanamino)butane dihydrochloride (IEM-1913) has important advantages over clinically employed monocationic 3,5-dimethyl-1-aminoadamantane (memantine) because its anticonvulsant activity is significantly greater and its therapeutic index is 814 times higher than that of memantine. 1-Amino-4-(3,5-dimethyl-1-adamantanamino)butane dihydrochloride (IEM-2127) and 1-amino-6-(3,5-dimethyl-1-adamantanamino)hexane dihydrochloride (IEM-2121) have anticonvulsant activity equal to that of memantine although their therapeutic indices are 94.9 and 88.6 times, respectively, greater than that of memantine. IEM-1913 causes statistically significant anticonvulsant effects in the dose range 0.03 – 0.3 mg/kg; IEM-2127 and IEM-2121, in the dose range 0.1 – 1.0 mg/kg, in contrast with memantine, which is effective only at a single maximum dose of 15 – 20 mg/kg. The high anticonvulsant activity and low toxicity of IEM-1913, IEM-2121, and IEM-2127 are explained by the fact that these bis-cationic compounds cause combined blocking of NMDA and AMPA brain receptors, in contrast with monocationic selective NMDA-blocker memantine.
Об авторах
V. Gmiro
Institute of Experimental Medicine
Автор, ответственный за переписку.
Email: gmiro2119@gmail.com
Россия, 12 Akad. Pavlova St., St. Petersburg, 197376
S. Serdyuk
Institute of Experimental Medicine
Email: gmiro2119@gmail.com
Россия, 12 Akad. Pavlova St., St. Petersburg, 197376
O. Veselkina
Vertex Pharmaceutical Company
Email: gmiro2119@gmail.com
Россия, 27-A 24th-Liniya, Vasil’evskii Ostrov, St. Petersburg, 199106
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