Androstane derivative devoid of anabolic-virilizing effects and endowed with an antiglucocorticoid activity.

2-Carbodecyloxy-17 alpha-methylandrosta-1,4-dien-11 beta,17 beta-dihydroxy-3-one (decylroxibolone, BR 917) is a new androstane derivative, esterified with decyl alcohol, carrying a methyl group in the 17 position, a hydroxyl group in the 11 beta position and a carboxyl group in position 2. Unlike norandrostenolone decanoate, decylroxibolone did not cause any weight increase of the levator ani muscle and of the seminal vesicles in castrated rats, nevertheless exerting a marked antiglucocorticoid activity. This new steroid agent can consequently act positively on the nitrogen metabolism, being concurrently devoid of undesired virilizing anabolic effect.

Novel pyrimidine and 1,3,5-triazine hypolipidemic agents.

New compounds were synthesized by changing the substituents of a trisubstituted pyrimidine, i.e., [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio] acetic acid, a potent hypolipidemic agent, impaired, however, by a marked hepatomegaly-inducing effect. The structural variations led to the subsidence (14b, i.e., 4-chloro-2-(dimethylamino)-6-[(2,3-dimethylphenyl)amino]pyrimidine) or to the reduction (18b, [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]amino] acetic acid) of said untoward effect but still maintained the hypolipidemic effect that, although markedly decreased, still proves significant for serum cholesterol and triglycerides (18b) or for serum triglycerides only (14b).

Pharmacokinetics of fentiazac in rats and monkeys.

Pharmacokinetic investigations were carried out on 2-phenyl-4-p-chlorophenyl-thiazol-5-ylacetic acid (fentiazac) in the rat and in the monkey. The drug, rapidly absorbed by the gastrointestinal system, shows a long maintenance in the body, with a long half-life in both animal species. The rate of biotransformation and the times of presence in the blood circulation of both unchanged drug and of its metabolites are indicated by the serum levels of cold fentiazac and labelled fentiazac. Urinary and fecal excretion attain levels amounting to 24 and 70%, respectively, of the dose administered.

Clofibrate, pirinixil (BR 931) and WY-14,643 do not affect body cholesterol in Sprague-Dawley rats.

Cholesterol levels in plasma and different tissues were determined in Sprague-Dawley male rats, on standard and cholesterol-cholic acid enriched diets, after short term treatment with the absorbable hypolipidemic agents, clofibrate, WY-14,643 and Pirinixil (BR 931). The objective of the study was to evaluate the mode of action of these drugs in decreasing plasma cholesterol, be it by increased tissue mobilization, or by redistribution from plasma to tissues. After one or two weeks on a standard diet, none of the three agents significantly affected total body cholesterol stores. In spite of the liver enlargement induced by all three, in no case was total liver cholesterol significantly raised. Only clofibrate significantly increased colonic cholesterol concentrations. On a cholesterol-cholic acid regimen, some cholesterol mobilization was noted with all three drugs. However, only Pirinixil significantly reduced total liver cholesterol as well as the estimated total body cholesterol. A parallel effect of diet and drugs on plasma and body cholesterol pools is not constantly observed. In the examined rat model, clofibrate and two chemically unrelated compounds with a probably similar mechanism of action, markedly reduce plasma cholesterol levels while not affecting or decreasing total body cholesterol stores.

Pharmacological profile of BR-931, a new hypolipidemic agent that increases high-density lipoproteins.

BR-931 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio-(N-beta-hydroxyethyl)-acetamide], a new hypolipidemic agent of low toxicity, was evaluated in several tests of lipolysis and hyperlipidemia in rats, and in the cholesterol-induced atherosclerosis in rabbits. Significant hypolipidemic activity was observed in rats with doses of the agent at 12.5--50 mg/kg. In the Triton-induced hyperlipidemia, 50 mg BR-931 per kg was equieffective as 200 mg of clofibrate (CPIB) per kg. In contrast with CPIB, BR-931 exerted a powerful antilipolytic activity against epinephrine, ACTH, nicotine and cold exposure. BR-931 was particularly effective in diet-induced hyperlipidemias. Ethanol lipemia was totally prevented by the agent at 100 mg/kg. With Nath's diet, doses as low as 25 mg/kg significantly reduced hypercholesterolemia and hypertriglyceridemia. In these last two tests, the distribution of lipoprotein cholesterol was also determined. CPIB did not affect HDL cholesterol levels that had been decreased by the diets; in contrast, BR-931, already at doses of 50 mg/kg, brought the HDL/total cholesterol ratio back toward normal. A significant HDL cholesterol increase, together with some reduction of atheromatosis, was also observed in cholesterol-fed rabbits. BR-931, a potent inducer of liver peroxisones and of mitochondrial carmitine acetyltransferase, appears to be a hypolipidemic agent of high efficacy and low toxicity for the clinical treatment of hyperlipidemias and atherosclerosis.

[Antiedema activity of a non-steroid physiological anti-inflammatory agent (author's transl)]. / Odemhemmende Aktivität einer steroidfreien, physiologischen, anti-inflammatorischen Substanz

The antiedema activity of experimental Lysoartrosi, a biological preparation, was demonstrated against edemas induced by carrageenin, formalin, dextran, serotonin, egg albumin and kaolin. Lysoartrosi, containing a mixture of polypeptides, is thus, the only preparation which is active against such a wide spectrum of inflammatory agents.