Imidazole fungicides provoke histamine release from mast cells and induce airway contraction.

The effects of imidazole fungicides on rat mast cells and on guinea-pig airway smooth muscle contraction were studied. The dose-effect studies on mast cells were performed to prove our hypothesis that imidazole fungicides are potential histamine releasing agents and thus may induce bronchoconstriction in vivo. Indeed, all imidazole fungicides tested (i. e. ketoconazole, miconazole, prochloraz) and an agricultural formulation of prochloraz (i. e. Sportak) were able to elicit histamine release from mast cells in the concentration range of 30-300 microM, although there were marked differences in potency and efficacy. The in vivo experiments clearly showed that inhaled Sportak aerosols induce a significant bronchoconstriction in guinea-pigs. Moreover, after a single 5 min exposure to Sportak aerosols the animals developed airway hyperreactivity against histamine. From the results of our study it may be concluded that certain imidazole fungicides provoke histamine release by a non-immunological mechanism, induce airway constriction in guinea-pigs and hence may be harmful to spray operators who might inhale fungicide aerosols used for plant protection.

[Greater oral activity of etilefrine pivalate compared to etilefrine in the cat and dog]. / Höhere orale Wirksamkeit von Etilefrinpivalat im Vergleich zu Etilefrin bei Katze und Hund.

Etilefrine pivalate (K 30 052, Ep) and etilefrine (E) were compared in regard to their effects on the circulation of cats and dogs and in regard to their effects on isolated organs (papillary muscles, atria, vena cava caudalis) of guinea pigs and rabbits. The effects of Ep and E were qualitatively equal. Ep was less effective than E on isolated organs and after intravenous injection, it was however more effective after oral or intraduodenal application. This result is in line with the hypothesis that Ep is inactivated during the first-pass to a smaller extent than E and is split after absorption to E and pivalinic acid.

[On the spasmolytic action of 3-butoxy-1-phenoxy-propanol-(2) (febuprol) on the biliary tract (author's transl)]. / Zur spasmolytischen Wirkung von 3-Butoxy-1-phenoxy-propanol-(2) (Febuprol) auf des Gallengangsystem.

The spasmolytic activity of 3-butoxy-1-phenoxy-propanol-(2) (febuprol) on the biliary tract is demonstrated in two different experimental arrangements in anesthetized dogs. This effect on the spasm provoked by morphine or prostigmine is illustrated by measuring the alteration of pressure in the choledochal duct. The spasmolytic efficacy of febuprol is significant and indicates a favourable secondary therapeutic effect of this substance.

[On the pharmacodynamics of alpha- and beta-escin after oral application (author's transl)]. / Zur Pharmakodynamik von alpha- und beta-Aescin nach Applikation per os

Contrary to the almost water insoluble crystalline beta-escinic acid, the water soluble forms of escin -- such as alpha-escinic acid or its salts, Na-b-escinate and the amorphous beta-escinic acid -- are so well absorbed by the gastro-intestinal tract that the effects after oral application could be compared with those of the reference substances furosemide, hydrocortisone, acetylsalicylic acid, azapropazone and phenylbutazone. Escin was tested in the stasis edema, cotton-pellet-granuloma, and UV-erythema, i.e., in test models which seem specially suited to characterize the properties of this substance. In these tests which reflect both the prophylactic and the therapeutic treatment escin has proven antiexudative-antiphlogistic effects. They are based on a favorable influence of permeability and diuresis.