The mechanism of the hypothermic effect of amantadine in rats and mice

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Abstract
Amantadine (25–100 mg kg−1, i.p.) given to rats at an ambient temperature of 4°, or mice at 21°, 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.