The mechanism of the hypothermic effect of amantadine in rats and mice.
Amantadine (25--100 mg kg-1, i.p.) given to rats at an ambient temperature of 4 degrees, or mice at 21 degrees, caused a marked fall in rectal temperature. Prior administration of pimozide (1--2 mg kg-1, s.c.) did not block hypothermia due to amantadine in rats or mice; in contrast, hypothermia due to apomorphine (2 mg kg-1, i.p.) and piribedil (10--40 mg kg-1, i.p.) in rats was blocked by pimozide pretreatment. Amphetamine (5 mg kg-1, i.p.) given 2 h after reserpine (2 mg kg-1, i.p.) caused a reversal of the hypothermic effect of reserpine in mice, but a reversal was not obtained with amantadine (50 mg kg-1, i.p.). Direct injection of amantadine (4--8 mg kg-1) into the cerebral ventricles (i.c.v.) of mice caused marked hypothermia which was not blocked by pimozide, but intravenous injection of the same dose of amantadine did not cause hypothermia. Rimantadine, a congener of amantadine but without anti-parkinsonian activity, also caused pimozide insensitive hypothermia in mice at doses of 50 mg kg-1, intraperitoneally or 2--4 mg kg-1, intracerebroventricularly. The main conclusion drawn from these results is that in causing hypothermia amantadine acts in the cns but not on dopamine receptors.
D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D003864:Depression, Chemical; D003913:Dextroamphetamine / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D010868:Pimozide / Q000494:pharmacology; D010891:Piribedil / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013696:Temperature
D010868:Pimozide; D012110:Reserpine; D000547:Amantadine; D010891:Piribedil; D006220:Haloperidol; D003913:Dextroamphetamine