[2-Amino-oxazoles as potential H-bonding agents in virostatic research. 4. Pharmacokinetics and pharmacologic-toxicologic profile of 2-guanidino-4,5-dipropyloxazole hydrochloride]. / 2-Amino-oxazole als potentielle H-Brückenbildner in der Virostatika-Forschung. 4. Mitteilung: Pharmakokinetik und pharmakologisch-toxikologisches Wirkprofil von 2-Guanidino-4,5-dipropyloxazol-hydrochlorid.

Out of the group of 2-amino-oxazoles 1 was found to be the most potent antiviral compound. Following p.o. or s.c. administration to rats, the 14C-labeled 1 was quickly and completely absorbed. The TRA was eliminated mainly via the kidneys and the liver with half-lives between 32 and 42 h. The acute pharmacodynamic effects of 1 were decrease of blood pressure, bradycardia, and inhibition of both gastric emptying and acid secretion. On smooth muscles spasmolytic and alpha-anti-adrenergic actions were predominant. After single administration the following MTD's were determined: 30 (mouse), 20 (rat), 10 mg/kg i.v. (pig), and 500 (mouse, rat), greater than 100 mg/kg p.o. (pig), respectively. In a subchronic toxicity study in rats, oral doses of 1 between 15 and 240 mg/kg given daily for 4 weeks were tolerated without any severe alterations related to the drug.

[Use of direct calorimetry for continuously following the course of experimental infections in the mouse]. / Anwendung der direkten Kalorimetrie zur kontinuierlichen Verfolgung experimenteller Infektionsverläufe bei der Maus.

To obtain information about early symptoms of infection measurements of heat production were performed in experimentally infected animals. As a model Mengo virus-infected mice were used. Construction and physical properties of the flow calorimeter device are described. Fever was not detected by method used. However, deviations from normal behaviour of the animals were demonstrated as a result of the relationship between motoric activity and heat produced. Furthermore, the method may be particularly useful for the determination of the exact time of death, which is of interest for mathematical modelling of survival data (RECKNAGEL et al. 1986; GUTHKE et al. 1987; SUHNEL und VECKENSTEDT 1989).

Pharmacological activities of the progestin STS 557.

This paper reports on pharmacological properties of 17 alpha-cyano-methyl-17 beta-hydroxy-estra-4, 9-dien-3-one (STS 557), which were obtained from basic screening investigations. At high doses (100 mg/kg i.p.) STS 557 was sedatively active on the CNS, but did not show any narcotic or anticonvulsant activities. A hypothermic effect of STS 557 was found at non-sedative i.p. or oral doses in mice and rats. This was also shown for the standard levonorgestrel, doubtlessly to a lesser extent. The cardiovascular system as well as the renal excretion of urine and electrolytes were unaffected by the test compound. STS 557 was found to stimulate the spontaneous motility of the isolated rat uterus dose-dependently; an antiprogesteronic activity seems to be unlikely. STS 557 did not show any glucocorticoid or antiexudative properties. At oral dose levels of 10 and 50 mg/kg (X 4 days), STS 557 and levonorgestrel caused similar changes in the serum lipids of normolipidemic and hyperlipidemic rats. The concentration of total cholesterol was decreased, that of the FFA was increased. The triglycerides were lowered only in hyperlipidemic animals. All the pharmacological effects of STS 557 appeared at high doses, much higher than te proposed therapeutic ones.