Erlotinib: Lacking of Cholinergic Effects on Tracheal Smooth Muscle

Abstract

Erlotinib (Tarceva) is an oral epidermal growth factor receptor-tyrosine kinase inhibitor that is mainly used for patients with advanced or metastatic non-small-cell lung cancer. Tyrosine kinase signaling cascades also play a critical role in the pathogenesis of allergic airway inflammation and airway remodeling. However, cholinergic effects caused by erlotinib on tracheal smooth muscle remain unclear. The objective of this study was to determine the effects of erlotinib on the isolated rat tracheal smooth muscle in vitro . To examine the cholinergic effects of erlotinib, in vitro rat tracheal smooth muscle was used to assess alterations in methacholine-induced contraction (served as a parasympathetic mimetic) and electrically induced contraction. The results demonstrated that the addition of erlotinib (from 1 × 10 −8 M to 1 × 10 −4 M) induced no significant effects on tracheal tension after methacholine treatment. Furthermore, erlotinib did not affect electrical field stimulation-induced spike contraction. This study demonstrated that erlotinib had no cholinergic effects in vitro , suggesting it may be safe for asthmatic patients with non-small-cell lung cancer after further investigation.