5-sulfamoylorthanilic acids, a sulfonamide series with salidiuretic activity.

A series of 4,N-disubstituted 5-sulfamoylorthanilic acids was synthesized by nucleophilic substitution reactions starting either from 2,4-dihalogeno-5-sulfamoylbenzenesulfonic acids or, in most cases, from phenyl 2,4-dihalogeno-5-sulfamoylbenzenesulfonates. The latter method is based on the relative stability of the phenoxysulfonyl group to nucleophiles, e.g., amines, phenols, and thiols, and the possibility of smooth hydrolytic or hydrogenolytic cleavage as a final step, with formation of the SO3H group. On evaluation of these compounds for salidiuretic activity in rats orally (po), and in dogs orally and intravenously (iv), a number of highly active substances was found; the best had a threshold dose of 0.02 mg/kg po in dogs. The results are given in tables, and the structure-activity relationships within the series are discussed. Besides the known effect of the phenoxy radical, an outstanding activating effect was shown by the butylsulfonyl and cycloalkylsulfonyl radicals and by the N-methylanilino radical in particular when they were located in the 4-position of the orthanilic acid molecule. The sulfanilic acid isomers corresponding to three of the most active compounds were synthesized and proved to be completely inactive in rats.

[Pharmacokinetic problems in surgery]. / Chirurgie und Pharmakokinetik.

The article deals with the shortcomings of pharmacokinetic models in predicting tissue-concentrations of drugs. Several examples are shown from our group that cooperation of surgeons and pharmacokinetic researchers is necessary to overcome these shortcomings.

Measurements of oxygen tension from the canine gastric mucosa under the influence of vasoactive and acid stimulating agents and following vagotomy. Implications on the pathophysiology of peptic ulceration.

By the use of a multiwire platinum electrode mucosal tissue pO2 from the canine gastric antrum is continuously recorded. Injection of norepinephrine causes a short, steep fall of mucosal pO2, naftidrofuryl elevates mucosal pO2 for several minutes in spite of reduced arterial blood pressure, pentagastrin produces a biphasic response, a temporary rise of mucosal pO2 is followed by a longer lasting decrease, vagotomy causes a considerable and more persistent drop of mucosal pO2. These experimental findings are discussed in their possible relations to the clinical problem of ulcer formation and therapy of gastroduodenal bleeding.

Method of collecting urine and comparative investigation of quantities excreted by cats and dogs after administration of furosemide.

A method is described for precise investigation of diuresis and saluresis in cats, using trained animals in a special diuresis apparatus. Furosemide given intramuscularly (IM) to cats at the dose level of 10 mg/kg produced slight untoward reactions of short duration. Therefore, this dose lies at the upper limit of tolerance. Saluretic and diuretic effect of 5 different doses of furosemide was investigated in 4 cats and 20 dogs. A dose-dependent increase in diuresis was achieved in cats given doses of furosemide ranging from 1.25 to 10 mg/kg. In the dog, the range of effectiveness was broader. In both species, there was a parallel increase in the excretion of sodium and chloride ions. The excretion of potassium ions in the cat remained unaffected, whereas in the dog, there was a dose-dependent increase in potassium ion excretion, which became especially distinct when large doses were given. A direct comparison of total saluretic and diuretic values in the dog and cat after IM administration of furosemide was not possible, since the calculated straight lines had different slopes, and their points of intersection lay outside the scope of this study. A difference can be assumed to exist between dog and cat in the mode of action of diuresis and saluresis after administration of furosemide.