Summary
On each nitrogen atom of 3H-hexamethonium one methyl group was replaced either by a n-propyl, N-n-propylphthalimide or n-nonyl group. By means of whole-body autoradiography the influence of the different substituents on the distribution pattern was studied in mice after i.v. or s.c. injection. Increasing the chain length of the substituents caused an enhanced accumulation of the respective compounds into secreting tissues, heart muscle, and liver, and an augmentation of biliary excretion. The affinity of the bis-quaternary ammonium compounds for cartilaginous tissues was also altered. The physiological “barriers” between blood and brain or blood and the aqueous humor of the eye, were highly effective against the compounds studied, whereas the placenta could be penetreted by these derivatives.
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References
Ashgar, K., Roth, L. J.: Distribution of hexamethonium and other quaternary ammonium compounds in cartilage. J. Pharmacol. exp. Ther. 176, 83–92 (1971).
Gerlach, F. D., Lüllmann, H., Ohnesorge, F. K., Wassermann, O.: Beziehungen zwischen anticholinerger Wirkung und Struktur bei Alkan-α, ω-bis-ammonium-Verbindungen. Arzneimittel-Forsch. 20, 751–754 (1970).
Lauterbach, F.: Werden quaternäre Ammoniumverbindungen über einen enteralen Sekretionsmechanismus resorbiert? Naunyn-Schmiedebergs Arch. Pharmak. 266, 388–389 (1970).
Lüllmann, H., Ohnesorge, F. K., Schauwecker, G.-Ch., Wassermann, O.: Inhibition of the actions of carbachol and DFP on guinea-pig isolated atria by alkane-bisammonium compounds. Europ. J. Pharmacol. 6, 241–247 (1969).
Lüllmann, H., Ohnesorge, F. K., Tonner, H. D., Wassermann, O., Ziegler, A.: Influence of alkane-bis-ammonium compounds upon the activity of the AChE and upon its inhibition by DFP. Biochem. Pharmacol. 20, 2579–2586 (1971).
Ullberg, S.: Studies on the distribution and fate of 35S-labelled benzylpenicillin in the body. Acta radiol. (Stockh.) Suppl. 118 (1954).
Wassermann, O.: Untersuchungen über die Verteilung von 3H-markiertem Hexamethonium im Organismus mittels der Ganztierschnitt-Technik. Naunyn-Schmiedebergs Arch. Pharmak. 266, 473 (1970).
Wassermann, O.: Influence of substituents on pharmacokinetics of bis-quaternary ammonium compounds. Naunyn-Schmiedebergs Arch. Pharmak. 270, (Suppl.) R 154 (1971 b).
Wassermann, O.: Studies on the pharmacokinetics of bis-quaternary ammonium compounds. I. Synthesis, physicochemical properties and protein binding of 3H-labelled hexamethonium and some of its derivatives. Arzneimittel-Forsch. (Drug Res.) (in press) (1972).
Wassermann, O.: Studies on the pharmacokinetics of bis-quaternary ammonium compounds. II. Autoradiographic studies on the distribution of 3H-hexamethonium in mice. Naunyn-Schmiedebergs Arch. Pharmak. 270, 419–427 (1971a).
Young, I. M.: The placental transfer of hexamethonium bromide in the rabbit and its appearance in the amniotic fluid. J. Physiol. (Lond.) 116, 4P-5P (1951).
Young, I. M.: The placental transfer of hexamethonium bromide and the origin of amniotic fluid in the rabbit. J. Physiol. (Lond.) 122, 93–101 (1953).
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Wassermann, O. Studies on the pharmacokinetics of bis-quaternary ammonium compounds. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 251–261 (1972). https://doi.org/10.1007/BF00500054
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DOI: https://doi.org/10.1007/BF00500054