[Background/Aims]

One of the strategies for creating new pharmacologically active compounds is the use of a central scaffold and the addition of various substituents to it. The diazabicyclic molecule bispidine represents a promising basis for chemical modifications and synthesis of compounds with diverse biological activities. In this work, the actoprotective effect of N, N-disubstituted bispidine derivatives containing monoterpene substituents is shown for the first time. The present work evaluated the actoprotective activity, locomotor and anxiety-like behavior in mice, and the effect on the cholinergic system in the central nervous system. Bromantane was used as a reference drug.

[Results]

The results showed that compounds combining bispidine scaffold and monoterpenoid fragments exhibit actoprotective effect in tests on a treadmill and swim with a load of 10% of body mass, increasing the duration of physical work. In the "Open field" test, which determines the locomotor and anxiety-like behavior in mice, it was found that some disubstituted derivatives significantly increased the distance and residence time of animals in the center of the open field compared to intact controls, which may indicate a stimulating effect on the central nervous system and a possible anxiolytic effect.

As a result, compounds combining fragments of a monoterpenoid and 3,7-diazabicyclo[3.3.1]nonane (bispidine) core exhibit actoprotective activity, acting on various neurotransmitter systems.

This work was supported by RFBR Grant 18-03-00437.