Effect of a kynurenic acid analog on home-cage activity and body temperature in rats.
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.
Gedeon Richter Plc, Pharmacology and Drug Safety Department, Budapest, Hungary; MTA SE NAP B Cognitive Translational Behavioral Pharmacology Group, Budapest, Hungary. Electronic address: kassai.ferenc@med.semmelweis-univ.hu.
Ferenc
F
Kassai
Gedeon Richter Plc, Pharmacology and Drug Safety Department, Budapest, Hungary.
Rita
R
Kedves
Gedeon Richter Plc, Pharmacology and Drug Safety Department, Budapest, Hungary; MTA SE NAP B Cognitive Translational Behavioral Pharmacology Group, Budapest, Hungary.
István
I
Gyertyán
MTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, Hungary.
Bernadett
B
Tuka
Institute of Pharmaceutical Chemistry and Stereochemistry Research Group of the Hungarian Academy of Sciences, University of Szeged, Szeged, Hungary.
Ferenc
F
Fülöp
Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary.
József
J
Toldi
Gedeon Richter Plc, Pharmacology and Drug Safety Department, Budapest, Hungary.
Balázs
B
Lendvai
MTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, Hungary; Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary.
László
L
Vécsei
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004361:Drug Tolerance; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats
D018696:Neuroprotective Agents; C533052:SZR 72; D007736:Kynurenic Acid
Home-cage activity; Hypothermia; Kynurenic acid; Kynurenic acid analog; Telemetry