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Arzneimittelbedingte Hyposiderämie bei ratten

Drug induced hyposideremia in rats

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Abstract

Four hours following a single dose of 25 mg/kg of d, 1-Amphetamine in rats, a 40 to 60 % drop of plasma iron level occurred. This reaction cannot be explained by the Amphetamine-induced rise in body temperature and motor activity, since when pretreated with α-Methyltyrosine, Chlorpromazin, Haloperidolum, Guanethidin and Reserpin this was not observable.

All the drugs applied for pretreatment in adequately high doses also induced hyposideremia. Four hours following a single dose of 200 mg/kg of α-Methyltyrosine, plasma iron level was reduced by 55 %, after 10 mg/kg of Chlorpromazin by 11 %, after 5 mg/kg of Haloperidolum by 28 % and after 20 mg/kg of Guanethidin by 50 %. The most pronounced effect (69 % fall) was obtained by 20 hour pretreatment with 20 mg/kg of Reserpin.

As possible pathomechanism of the drug induced hyposideremia the applied drugs may be regarded as “non-specific stressfull agents”, or as another possibility, the detoxifying mechanism in RES induced by toxic concentrations of the applied drugs can be considered as responsible for this phenomena.

Zusammenfassung

4 Std nach einmaliger Gabe von 24 mg/kg d,l-Amphetamin i.p. kommt es bei Ratten zu einem Abfall des Eisens im Plasma um 40 bis 60 %. Die Reaktion ist nicht mit dem amphetaminbedingten Anstieg von Körpertemperatur und Skeletmuskelarbeit zu erklären, da sie durch Vorbehandlung mit α-Methyltyrosin, Chlorpromazin, Haloperidol, Guanethidin und Reserpin nicht unterdrückt werden kann.

Jedes der zur Vorbehandlung verwandten Medikamente löst selbst bei entsprechend hoher Dosierung eine Hyposiderämie aus. 4 Std nach einmaliger Gabe von 200 mg/kg α-Methyltyrosin vermindert sich der Eisenspiegel im Plasma um 55 %, nach 10 mg/kg Chlorpromazin um 11 %, nach 5 mg/kg Haloperidol um 28 % und nach 20 mg/kg Guanethidin um 50 %. Dieser Effekt ist am ausgeprägtesten mit einer Plasmaeisenverminderung um 69 % 20 Std nach Gabe von 20 mg/kg Reserpin.

Als möglicher Pathomechanismus der arzneimittelbedingten Hyposiderämie wird die Wirkung der untersuchten sämtlich zentralnervös aktiven Medikamente als “non-specific stressfull agents” sowie der durch ihre toxische Konzentration in Gang gesetzte Entgiftungsmechanismus im RES diskutiert.

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Schäfer, I., Elek, S. Arzneimittelbedingte Hyposiderämie bei ratten. Arch Toxicol 30, 187–198 (1973). https://doi.org/10.1007/BF02426042

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