Investigation of the spasmolytic activity of the flavonoid fraction of Achillea millefolium s.l. on isolated guinea-pig ilea.

The spasmolytic activity of a flavonoid fraction of a commercial sample of yarrow (Achillea millefolium s.l.), its main flavonoids as well as quercetin and two flavonoid metabolites were investigated on isolated terminal guinea-pig ilea. The aglycones quercetin, luteolin and apigenin exhibited the highest antispasmodic activities with IC50 values of 7.8 micromol/L, 9.8 micromol/L and 12.5 micromol/L, respectively. Rutin and the flavonoid metabolites homoprotocatechuic acid and homovanillic acid showed no significant effects on contractility of the terminal ilea. From the results on the spasmolytic activity of the flavonoid fraction, the glycosides and the respective aglycones it is concluded that in tea prepared from yarrow the concentration of the flavonoids is high enough to exert a spasmolytic effect in the gut, which is mainly caused by blockade of the calcium inward current, but additionally also by mediator-antagonistic effects.

Synthesis and pharmacological profile of non-peptide vasopressin antagonists.

Recently we presented a series of 6-ethyl and 6-benzylthieno[2,3-b][1,4]thiazine derivatives with relaxing effects on vascular smooth muscle and terminal ileum. In this report the synthesis of further thieno[2,3-b][1,4]thiazine derivatives and related compounds with a thieno[2,3-b][1,4]thiazepine or thieno[3,2-b][1,4]thiazine ring system is described. The pharmacological effect of the agents was tested in isolated smooth (terminal ileum, pulmonary artery, aortic rings, myometrial strips) and heart (papillary muscle, spontaneously beating right atrium) muscle preparations of the guinea pig. Contractions were measured isometrically, and smooth muscle preparations were either precontracted with high K+ (60 or 90 mM KCl containing nutrient solution) or with agonists, while papillary muscles were electrically stimulated (1 Hz). The vasopressin antagonistic activity of the test compounds was tested in isolated papillary muscles in which the V1A-receptor subtype is located. The biphasic response to vasopressin was antagonized, dependent on the chemical structure of the test compound. Thieno[3,2-b][1,4]thiazines were more potent than thieno[2,3-b][1,4]thiazine and thieno[2,3-b][1,4]thiazepine compounds. In addition, substitution of a methyl substituted terminal benzyl ring instead of a phenyl- or dichlorobenzoyl moiety attenuated the vasopressin antagonistic effect.

Investigation of the electrophysiological properties of enniatins.

Enniatins are cyclohexadepsipeptides produced by various species of the genus Fusarium, and are known to have ionophoric, antibiotic, and in vitro hypolipidaemic properties. With the patch clamp technique in the inside-out mode it could be shown that enniatin easily incorporates into the cell membrane in which it forms cation-selective pores. This feature is characterized by unitary transitions to conductance levels typical for channels, ion selectivity, rectification, conductivity in the pS range, and block. A model of vertically stacked enniatin molecules that form sandwich complexes is suggested. Like gramicidin enniatin is a passive channel. Single channel properties for the isomers enniatin A1, B, and B1 differed from each other. This implies an influence of the substituted moieties on the complexation of cations. Electrical activity was followed by changes in intracellular ion concentrations, which are consistent with depolarization of the membrane resting potential, shortening of action potential duration, and reduced contractility.