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RESEARCH PRODUCT

Die Beziehung zwischen der Guanethidin-Konzentration im Rattenherzen und dem Noradrenalingehalt

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Guanethidine was intravenously injected into rats and was subsequently determined in the hearts by extracting the tissue with trichloroacetic acid, purifying the extracts on cation exchange columns and by paper chromatography, and coupling the guanethidine with ninhydrin in alkaline solution before fluorimetric estimation. The concentration in the heart reached a maximum of 9 μg/g within 15 min of injecting 15 mg/kg, and was still 6.2 and 5.7 μg/g after 1 and 3 hours, respectively. Guanethidine caused a decrease of the heart noradrenaline concentration, measured fluorimetrically, by 56% in 3 hours and by 93% in 14 hours. The adrenaline concentration was likewise decreased. A metabolite with the guanidium group still intact was contained in the eluates of the ion exchange columns, but was separated from guanethidine by paper chromatography. The metabolite was detectable in heart extracts as soon as 6 min after injection of the drug, and the ratio of metabolite to guanethidine was then identical in heart and blood. The proportion in the heart rose steadily with time after injection, being about 50% after 3 hours. By this time 10–15% of the guanethidine administered had been excreted unchanged in the urine in addition to the metabolite mentioned. The results indicate that guanethidine is rapidly concentrated and firmly held in the heart throughout the period of noradrenaline depletion.