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Pharmaceutical Chemistry Journal

, Volume 52, Issue 10, pp 830–834 | Cite as

Synthesis and Pharmacological Properties of Adamantane-Containing Bis-Cationic Compounds

  • V. E. GmiroEmail author
  • S. E. Serdyuk
  • O. S. Veselkina
Article
  • 35 Downloads

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.

Keywords

memantine IEM-1913 IEM-2121 IEM-2127 seizures 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • V. E. Gmiro
    • 1
    Email author
  • S. E. Serdyuk
    • 1
  • O. S. Veselkina
    • 2
  1. 1.Institute of Experimental MedicineSt. PetersburgRussia
  2. 2.Vertex Pharmaceutical CompanySt. PetersburgRussia

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