Astemizole, an inhibitor of ether-à-go-go-1 potassium channel, increases the activity of the tyrosine kinase inhibitor gefitinib in breast cancer cells

Abstract Background Expression and activity of the potassium channel ether-à-go-go-1 (EAG1) are strongly related to carcinogenesis and tumor progression, which can be exploited for therapeutic purposes. EAG1 activity may be reduced by preventing its phosphorylation with epidermal growth factor receptor (EGFR) kinase inhibitors and by astemizole, which blocks the channel pore and downregulates its gene expression. Objective We aimed to study the potential cooperative antiproliferative effect of the EGFR inhibitor gefitinib and the EAG1-blocker astemizole, in breast cancer cells. Materials and Methods The cells were characterized by immunocytochemistry. Inhibitory concentrations were determined by non-linear regression analysis using dose-response curves. The nature of the pharmacological effect was evaluated by the combination index equation while cell cycle analysis was studied by flow cytometry. Results Astemizole and gefitinib inhibited cell proliferation in a concentration-dependent manner, with inhibitory concentrations (IC 50) values of 1.72 µM and 0.51 µM, respectively. All combinations resulted in a synergistic antiproliferative effect. The combination of astemizole and gefitinib diminished the percentage of cells in G2/M and S phases, while increased accumulation in G0/G1 of the cell cycle. Conclusions Astemizole and gefitinib synergistically inhibited proliferation in breast cancer cells expressing both EGFR and EAG1. Our results suggest that the combined treatment increased cell death by targeting the oncogenic activity of EAG1.

Evaluación comparativa del astemizol-pseudoefedrina y loratadina-pseudoefedrina en niños con rinitis alérgica / Evaluated comparative the effectiveness and safety of astemizole-pseudoephedrine to loratadine-pseudoephedrine in the treatment of allergic rhinitis

Se realizó un estudio con el propósito de evaluar la eficacia y la tolerancia de la solución astemizol-pseudoefedrina en comparación con el jarabe loratadina-pseudoefedrina en el tratamiento de la rinitis alérgica. Se incluyeron 50 niños de uno y otro sexo (34 varones y 16 mujeres) de edades entre 2 y 7 años que se asignaron al azar a cada grupo. Los pacientes se evaluaron antes, a los 3 y los 7 días de tratamiento. Los niños tratados con astemizol-pseudoefedrina obtuvieron mejores resultados, con efectividad promedio de 48 por ciento contra 64 por ciento de loratadina-pseudoefedrina. La diferencia fue significativa a favor de astemizol-pseudoefedrina para los síntomas oculares según las evaluaciones del médico y para la obstrucción y el prurito nasal y el estornudo según el diario del paciente. Ambos medicamentos comenzaron su acción antes de 30 minutos de administrados; a las 4 horas 38 por ciento de los pacientes del grupo tratado con astemizol-pseudoefedrina refirieron alivio contra 16 por ciento del grupo loratadina-pseudoefedrina. Un paciente del primer grupo y tres del segundo presentaron efectos secundarios

Evaluation of antimuscarinic activity in human volunteers: a teaching aid in clinical pharmacology.

The antimuscarinic activity of oxyphenonium bromide, diphenhydramine hydrochloride and astemizole were evaluated in six volunteers. The parameters used were salivary secretion, heart rate and pupillary size. The results indicated that the changes in heart rate and pupillary size and measurements were not convenient parameters for class room demonstration. However, salivary secretion and dryness of mouth were found to be reliable parameters for measurement. It was concluded that simple procedures like evaluation of antimuscarinic activity could be introduced as teaching aids in clinical pharmacology for undergraduate students.