[Anti-inflammatory and analgesic actions of of long-chain phenyl substituted alpha-aminoketones]. / Antiphlogistische und analgetische Wirkungen von längerkettigen phenylsubstituierten alpha-Aminoketonen.

The investigated phenyl substituted alpha-amino ketones have anti-inflammatory and analgesic activities as could be shown in animal models (rats and mice). The effectiveness depends on the length of the alkyl chain. After i.p. application the most active amino ketones are ten times more effective than acetyl salicylic acid, but the activity did not reach that of indomethacin. The effective analgesic dose is ten times lower than that for anti-inflammatory action. Including the results of the toxicity the analgesic efficiency of the amino ketones could be lead to substances with high analgesic activity. After oral administration only in high doses anti-inflammatory and analgesic effectivities were found. The structural analog keto group instead of the ester or amid group leads not to the expected increase in p.o. effectivity.

[Acute cocaine intoxication with fatal outcome]. / Akute Cocain-Intoxikation mit tödlichem Ausgang.

The clinical course and some toxicologic-analytical aspects of an acute intoxication with cocaine are presented. Diagnosis was made by the induced toxicologic emergency investigation since neither symptoms nor clinical test results or anamnestic data showed relevant diagnostic information. Based on the results of the analytic investigation, we concluded it was a suicide based on long-term abuse of cocaine. Because of the unusually high concentrations of cocaine und cocaine metabolites in the body of liquids and tissues, it seemed probable that the patient was intoxicated with a lethal dose of at least 1 g cocaine. This case report underlines the importance of clinical and toxicological investigations in the diagnostic procedure of unclear comata and the importance of forensic toxicological analysis in clarifying anamnestic questions.

On the mode of action of antiphlogistically active DL-omega-phenyl amino acid esters.

DL-omega-phenyl amino acid esters turned out to be inhibitors of the sheep vesicular gland prostaglandin H synthase in addition to their antiphlogistic action on the carrageenan-induced oedema of the rat paw and weak antihistaminic actions. The inhibition of the prostaglandin H synthase was dose-dependent, the inhibitory potencies were however much lower than that of indomethacin. Some but not all derivatives, such as DL-4-amino-4-phenylbutyric acid octyl ester, also caused inhibition of the pure lipoxygenase from rabbit reticulocytes and the conversion of arachidonic acid to leukotriene B4 and 5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid by human polymorphonuclear leukocytes as well as inhibition of antigen-induced release of histamine from mast cells of ovalbumin-sensibilized rats. Since no clear relations between the data of the in vitro and in vivo models were obtained, further studies on the pharmacokinetics and possible biotransformations are required.

[The pharmacologic activity of p-substituted DL-2-phenylglycine octyl esters]. / Zur pharmakologischen Wirksamkeit p-substituierter DL-2-Phenylglycinoctylester.

DL-2-phenylglycine octyl ester has antiphlogistic, analgesic and spasmolytic activities as shown in different animal models. The antiphlogistic effectiveness is changed only a little by the p-substitution at the phenyl ring, whereas the analgesic action is markedly influenced. Most of the substituted compounds are significantly more active than the unsubstituted ester. DL-2-(benzyloxyphenyl)glycine octyl ester is the most active compound, it has furthermore the highest therapeutic quotient. Using the i.p. application its efficacy exceeds that of acetylsalicylic acid, phenylbutazone and indometacin, respectively. The spasmolytic activity is differently changed by the substituents. The most active ester, DL-2-(p-methoxyphenyl)glycine octyl ester, is about two times more active than papaverine. In histamine induced spasm the effectiveness is low compared with the specific antagonist mepyramine. The results obtained show that the activities of the p-substituted DL-2-phenylglycine octyl esters are different with regard to the three investigated pharmacological properties.

[The synthesis of P-substituted DL-2-phenylglycine octylesters]. / Zur Synthese p-substituierter DL-2-Phenylglycinoctylester.

9 Titel compounds (p-RC6H4)CH(NH2.HCl)COO (CH2)7CH3 [R = F, Cl, HO, CH3O, CH3(CH2)3O, C6H5CH2O, CH3, (CH3)2CH and (CH3)2N.HCl] were obtained by esterification of p-substituted DL-2-phenylglycines with octanol either in the presence of dry hydrogen chloride (procedure A) or with thionyl chloride (procedure B). The advantages of the procedure B are the mild conditions, the more pure products, the possibility of esterification of diamino acids, and the stability of alkoxy groups as substituents. The synthesized octylesters are potential antiinflammatory and analgesic substances with spasmolytic activity.