Hyperpyrexia as a Contributory Factor in the Toxicity of Amphetamine to Aggregated Mice

Abstract

A rise of body temperature into a range lethal to mice preceded death in groups of mice injected with amphetamine sulphate. At dose levels from 8.8 to 66.7 mg/kg, mortality was associated with the extent of rise in body temperature of the mice, irrespective of the actual dose administered. Isolated mice given comparable doses of amphetamine also showed a marked increase in body temperature. However, except in a very few cases, it did not rise into the range found to be lethal. Amphetamine was more toxic to isolated mice subjected to foot-shock than to isolated mice housed under normal conditions. This has also been shown to be related to the extent of rise in body temperature of the mice. The effect of a number of substances on grouped amphetamine toxicity was investigated. Chlorpromazine and phenoxybenzamine partially antagonized the sharp rise in temperature following the administration of amphetamine, and also significantly reduced mortality. Calcium acetylsalicylate was without effect on the rise of body temperature or on mortality.Both the hypothermic compound 4-methyl-5-(,8-chlorethyl)-thiazole (S.C.T.Z.) and L-thyroxine sodium potentiated the rise in temperature and caused a significant increase in mortality.

General Pharmacology of Amphetamine-Like Drugs

“…Later, the hyperthermie effeet was described in rats (SIMONYI and SZENTGYÖRGI, 1949). Dose-and time-response relationships have been repeatedly reported in rats (BAAS, 1939;BRO-DlE et al, 1969;GESSA et al, 1969;RIVA et al, 1969;COPER et al, 1971;MATSUMOTO and GRIFFIN, 1971;YEHUDA and WURTMAN, 1972a;MAJ et al, 1972a;HAlOS and GARATTINI, 1973;BORBELY et al, 1974), in mice (AsKEw, 1962;DOLFINI et al, 1969a, b;CRAIG and KUPFERBERG, 1972;, and rabbits (HAFFNER, 1938;HAAS, 1939;HILL and HORITA, 1971;HORITA and HILL, 1973). Dose-and time-response relationships have been repeatedly reported in rats (BAAS, 1939;BRO-DlE et al, 1969;GESSA et al, 1969;RIVA et al, 1969;COPER et al, 1971;MATSUMOTO and GRIFFIN, 1971;YEHUDA and WURTMAN, 1972a;MAJ et al, 1972a;HAlOS and GARATTINI, 1973;BORBELY et al, 1974), in mice (AsKEw, 1962;DOLFINI et al, 1969a, b;CRAIG and KUPFERBERG, 1972;, and rabbits (HAFFNER, 1938;HAAS, 1939;HILL and HORITA, 1971;HORITA and HILL, 1973).…”

“…There is a hypothermia at ambient temperatures below + 15° C, and a potentiation of the hyperthermie response if the ambient temperature is inereased above + 20-+22 0 C up to +30-+37° C in rats (yEHUDA and WURTMAN, 1972a;BORBELY et al, 1974;SCHEEL-KRÜGER and HASSELAGER, 1974) and miee (ASKEW, 1962;DOLFINI et al, 1969a;CRAIG and KUPFERBERG, 1972). As deseribed in the introduetion to this seetion, the ambient temperature is of importanee for the body temperature response to amphetamine.…”

'Non-specific' mechanisms of neuronal damage in amphetamine neurotoxicity in the rodent striatum

“…Systemic administration of psychostimulants increases the core body temperature (Askew, 1962;Bowyer et al, 1992;Ali et al, 1994;Colado et al, 1998). Hyperthermia can result from an excessive release of dopamine.…”

Untersuchungen über die aminpotenzierenden Wirkungen von antidepressiv wirkenden Stoffen am Kaninchen

“…Parallel zur Mortalität der einzelnen und der gruppierten Maus verhält sich die Temperatursteigerung (1,9). Es kann deshalb angenommen werden, daß die erhöhte Aminfreisetzung entweder über eine Senkung der Wärmeabgabe (durch periphere Vasokonstriktion) oder durch eine Erhöhung der Wärmeproduktion (durch direkte calorigene Wirkung der frei gesetzten Amine) zum Tod durch Hyperthermie führe (13,29 La discussion des résu ltats aboutit à l'hypothèse que l'action de l'im ip ra m ine dans les expériences décrites ne soit pas duc îi une influence directe sur le lonus des centres végétatives m ais à une m odification des effets des amines biogènes dan s les organes périphériques de m êm e que dan s le centre.…”