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The anti-influenza drug oseltamivir evokes hypothermia in mice through dopamine D2 receptor activation via central actions

tetano

Editor, Senior Moderator
J Pharmacol Sci. 2017 Dec 15. pii: S1347-8613(17)30208-6. doi: 10.1016/j.jphs.2017.12.005. [Epub ahead of print]
[h=1]The anti-influenza drug oseltamivir evokes hypothermia in mice through dopamine D2 receptor activation via central actions.[/h] Fukushima A[SUP]1[/SUP], Fukui A[SUP]2[/SUP], Takemura Y[SUP]2[/SUP], Maeda Y[SUP]3[/SUP], Ono H[SUP]4[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Oseltamivir has a hypothermic effect in mice when injected intraperitoneally (i.p.) and intracerebroventricularly (i.c.v.). Here we show that the hypothermia evoked by i.c.v.-oseltamivir is inhibited by non-selective dopamine receptor antagonists (sulpiride and haloperidol) and the D[SUB]2[/SUB]-selective antagonist L-741,626, but not by D[SUB]1[/SUB]/D[SUB]5[/SUB]-selective and D[SUB]3[/SUB]-selective antagonists (SCH-23390 and SB-277011-A, respectively). The hypothermic effect of i.p.-administered oseltamivir was not inhibited by sulpiride, haloperidol, L-741,626 and SCH-23390. In addition, neither sulpiride, haloperidol nor SCH-23390 blocked hypothermia evoked by i.c.v.-administered oseltamivir carboxylate (a hydrolyzed metabolite of oseltamivir). These results suggest that oseltamivir in the brain induces hypothermia through activation of dopamine D[SUB]2[/SUB] receptors.


[h=4]KEYWORDS:[/h] Dopamine receptors; Oseltamivir; Thermoregulation

PMID: 29292053 DOI: 10.1016/j.jphs.2017.12.005
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