Background: N-(2-N,N-Dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride (SzR-72) is a kynurenic acid (KYNA) amide analog that displays neuroprotective action. Whereas its brain penetration ability and its solubility limit the therapeutic use of KYNA: the corresponding properties of the analog exceed those of the parent compound. Although SzR-72 has been extensively studied, its exact mechanism of action has not yet been fully clarified. As KYNA induces hypothermia in laboratory rodents, it may be hypothesized that SzR-72 may have a similar effect. This would be of major importance, since the hypothermia generated by external cooling is neuroprotective, thus a putative hypothermic effect of SzR-72 could contribute to its neuroprotective action.
Methods: The effects of SzR-72 on the body temperature and home-cage activity of rats were studied by using a telemetry system. In order to follow the longitudinal changes in the effects of the compound, subchronic drug administration was applied.
Results: The initial administration of the compound induced substantial hypothermia and reduced the home-cage activity. During the 5 days of SzR-72 administration, partial tolerance developed to the hypothermic effect, while the inhibition of home-cage activity detected after the acute administration was completely tolerated.
Conclusions: On the basis of these results, it cannot be excluded that the hypothermic effect of SzR-72 contributes to its neuroprotective action.
Keywords: Home-cage activity; Hypothermia; Kynurenic acid; Kynurenic acid analog; Telemetry.
Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.