THE COMPARISON OF THE PHARMACOLOGICAL ACTIVITY AND SAFETY OF BIS-AMMONIA ADAMANTANE-CONTAINING COMPOUNDS AND THEIR MONOAMMONIA ANALOGUE MEMANTINE

Abstract

The substance 1-amino-4-(1-adamantane-amino)-butane dihydrochloride (IEM-1913) has significant advantages over memantine, which is used in clinics, because the former exceeds the latter with regard to the antihypoxic, antiseizure, antidepressant, and analgetic activities being equivalent with regard to the antiparkinsonian activity and being less toxic and more safe in use. 1-Amino-6-(3,5-dimethyl-1-adamantane-amino)-hexane dihydrochloride (IEM-2121) and 1-amino-6-(3,5-dimethyl-1-ada- mantane-amino)-butane dihydrochloride (IEM-2127) are equivalent to memantine with regard to the antiparkinsonian, antiseizure, and antidepressant activities, but outperform memantine with regard to the antihypoxic and analgetic activities and are less toxic and more safe in use. At difference from memantine, which is effective only at the maximal doses of 15-20 mg/kg, IEM-1913 produced significant pharmacological effects at doses ranging from 0.03 to 1 mg/kg, and IEM-2121 and IEM-1227, at doses ranging from 0,3 to 3 mg/kg. The high pharmacological activities and low toxicities of IEM-1913, IEM-2121, and IEM-2127 are explained by the fact that, at difference from the mono-cationic selective NMDA blocker memantine, the above bis-cationic substances block both, NMDA and AMPA receptors in the brain.