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.
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.