Intracellular Binding of Terfenadine Competes with Its Access to Pancreatic ß-cell ATP-Sensitive K+ Channels and Human ether-à-go-go-Related Gene Channels.

Most blockers of both hERG (human ether-à-go-go-related gene) channels and pancreatic ß-cell ATP-sensitive K+ (KATP) channels access their binding sites from the cytoplasmic side of the plasma membrane. It is unknown whether binding to intracellular components competes with binding of these substances to K+ channels. The whole-cell configuration of the patch-clamp technique, a laser-scanning confocal microscope, and fluorescence correlation spectroscopy (FCS) were used to study hERG channels expressed in HEK (human embryonic kidney) 293 cells and KATP channels from the clonal insulinoma cell line RINm5F. When applied via the pipette solution in the whole-cell configuration, terfenadine blocked both hERG and KATP currents with much lower potency than after application via the bath solution, which was not due to P-glycoprotein-mediated efflux of terfenadine. Such a difference was not observed with dofetilide and tolbutamide. 37-68% of hERG/EGFP (enhanced green-fluorescent protein) fusion proteins expressed in HEK 293 cells were slowly diffusible as determined by laser-scanning microscopy in the whole-cell configuration and by FCS in intact cells. Bath application of a green-fluorescent sulphonylurea derivative (Bodipy-glibenclamide) induced a diffuse fluorescence in the cytosol of RINm5F cells under whole-cell patch-clamp conditions. These observations demonstrate the presence of intracellular binding sites for hERG and KATP channel blockers not dialyzable by the patch-pipette solution. Intracellular binding of terfenadine was not influenced by a mutated hERG (Y652A) channel. In conclusion, substances with high lipophilicity are not freely diffusible inside the cell but steep concentration gradients might exist within the cell and in the sub-membrane space.

[Cannabis for medicinal use: development of pharmacopoeia monographs as a quality standard]. / Cannabis für medizinische Zwecke: Entwicklung von Arzneibuchmonographien als Qualitätsstandard.

Herbal drugs and extracts, like all pharmaceutical starting materials used in the manufacture of medicinal products, must have an appropriate pharmaceutical quality. Corresponding quality standards are described in the individual monographs of the pharmacopoeia according to § 55 of the German Drug Law. This includes information on ingredients and active substance content, among other things. This article describes the development of the Cannabis Flower Monograph for the German Pharmacopoeia (DAB) and the quality requirements and storage conditions contained therein. The state of development of monographs for the European Pharmacopoeia is also presented.After it was announced that there would be new legal regulations for the medical use of cannabis flowers and cannabis extracts, the first work on the cannabis flower monograph for the DAB began as early as 2015. First, a monograph on cannabis flowers was published in May 2016 in the German Drug Codex (DAC). The monograph was replaced in May 2017 by the publication of the DAB monograph. A revised version of the DAB monograph has been in force since April 2018 as a national quality standard.A harmonised cannabis flower monograph for the European Pharmacopoeia is currently being prepared to replace national quality standards. In addition, the German Pharmacopoeia and subsequently the European Pharmacopoeia develops monographs for preparations from cannabis flowers. In future, harmonised monographs in the European Pharmacopoeia will make it possible to avoid multiple testing according to the respective national standards and to facilitate analyses in laboratories and pharmacies.

A triterpene ozonide from Senecio selloi.

From the dried and fresh aerial parts of Senecio selloi Spreng, De Candolle (Asteraceae), the new triterpene ozonide 1 was isolated. Its structure was elucidated by NMR experiments, including inverse techniques HMQC and HMBC and by synthesis from the precursor 2 In contrast to natural peroxides, no antiplasmodial activity was detected for the ozonide 1.

Screening of Brazilian plants for the presence of peroxides

Chloroform or dichloromethane extracts of 357 southern Brazilian plant species were tested for the presence of peroxides by thin-layer chromatography, using the spray reagent from Huber & Fröhlke. >From the species tested, 71 (20 por cento) showed positive results and most of them (56 por cento) are Asteraceae species. The species tested were mainly from Asteraceae, but 55 more families were screened, in a total of 77 genera surveyed...