Effects of Novel Heterocyclic Compounds LKHT 1-22 and LKHT 4-22 on Hippocampal Slices in Rats

Experiments on hippocampal slices in rats showed that novel heterocyclic compounds LKhT 1-22 and LKhT 4-22 (nicotinic acid derivatives) at the concentration of 5 mM inhibited orthodromic population responses in СА1 by 65  3 and 86  1 %, respectively. Comparison preparation mexicor (ethylmethylhydroxypyridine succinate) in the equal concentration also inhibited the responses by 54  3 %. Effects of LKhT 1-22 and LKhT 4-22 exceeded that of mexicor in 1.2 and 1.6 times, respectively. Besides, LKhT 4-22 was more effective than LKhT 1-22 in 1.3 times. Competitive AMPA receptor antagonist CNQX (1 µM) weakened the depressing effect of LKhT 4-22 in 1.2 times were markedly than LKhT 1-22, i.e. 73  1 % and 61  2 %, respectively. Also, in the presence of L-glutamate (0.75 М) LKhT 1-22 (5 µM) inhibited the evoked neuronal responses by 58  3 %, and LKhT 4-22 (5 µM) by 81  2 %. In its turn, CNQX weakened inhibition of the LKhT 4-22 evoked response in 1.1 times more markedly than LKhT 1-22, i.e. by 76  1 % and 67  2 %, respectively. It follows that LKhT 1-22 and LKhT 4-22 inhibit the synaptic transmission within the Schaffer collateral - СА1 pyramidal neurons. Moreover, LKhT 4-22 demonstrates a largely L-glutamatergic nature which is much less evident in LKhT 1-22. Involvement of AMPA glutamate receptors is highly important for effect of LKhT 4-22 and a bit less for LKhT 1-22. We can conclude that the hippocampus is crucial for the central effect of these novel compounds.