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Metabolic effects of N6-substituted adenosines in rats

Abstract In vitro studies using isolated fat cells of fed rats demonstrated that certain N 6 -substituted adenosine derivatives are highly effective antilipolytic agents. The compounds are thought to interfere with the binding of ATP to adenylate cyclase. Enzymatic reactions which provide or depend on ATP were not influenced. Substances which exhibit antilipolytic activity in vitro lowered serum free fatty acids (FFA) in normal rats after oral administration. No symptoms of tachyphylaxis were observed after oral treatment for four weeks. Blood glucose, cholesterol, triglycerides, corticosterone and adrenal wt were unaltered. Liver glycogen was decreased, presumably as a consequence of FFA depression. Isolated fat cells from treated animals exhibited a higher response towards added dibutyrylcAMP than controls. The mobilization of glucose from glycogen by glucagon in the anesthetized rat was not altered after treatment with tN 6 -substituted adenosines. Despite good tolerance after oral treatment, rats died after i.v. injections of low doses of adenosine derivatives, presumably of heart failure.

Effects of derivatives of indole carboxylic acids on carbohydrate metabolism of the rat

Abstract Several indole derivatives were characterized on their effects on carbohydrate metabolism in the rat and compared in their insulin-like effects on hepatic gluconeogenesis and glucose consumption in muscle with 5- O -methoxyindole-2-carboxylic acid (MICA) and with indole-3-butyric acid. The substances depressed blood glucose in the fasted adrenalectomized rat at an oral dose of 50–250 mg/kg. Glucose consumption in an isolated muscle preparation was altered only a small amount. In some cases glycogen content of muscle was reduced at a millimolar concentration. All compounds revealed strong inhibition of glucose production from pyruvate in isolated liver slices at a concentration of 10 −4 M. By chemical modification of the indole structure strong inhibitors of gluconeogenesis are obtained. It was not possible to find substances which show a high stimulation of glucose uptake and low activity in inhibiting gluconeogenesis.

Sulprostone (CP-34,089, ZK 57 671), a Prostaglandin E2 Analogue with Potent Antifertility Effects and Improved Selectivity for Uterine Smooth Muscles

PG E2 and PG F2α stimulate uterine smooth muscles and can be used for induction of abortion. The therapeutic potential is, however, reduced by their lack of tissue selectivity which results in a variety of side-effects.