Abstract
Local anesthetics, antimicrobial agents, and immunomodulatory therapeutics are increasingly being used in the clinic for major pain relief from surgeries, treatment of infections, and inhibiting inflammation. Local anesthetics bind to voltage-gated sodium ion channels (VGSC) to confer their activity. Fendiline shares chemical structural properties with local anesthetics and antibiotics. Fendiline is an L-type calcium channel blocker that was previously widely used to treat heart diseases and strokes. Since fendiline has structural similarities to local anesthetics, its VGSC blocking properties have not been fully elucidated. In addition, neither has fendiline’s antiviral, antibacterial, and immunomodulatory activity. The goal of this study was to determine if fendiline had potential as a local anesthetic, immunomodulator, and antimicrobial agent. These activities were evaluated in-vitro by assessing fendiline’s block of VGSCs in GH3 pituitary cells using patch-clamp electrophysiology, by assessing fendiline’s block of inflammation in both macrophages (RAW 264.7) and pituitary cells via proliferation and inflammatory marker assays, by assessing fendiline’s antiviral activities via viral cytopathic assays against vesicular stomatitis virus (VSV) in GH3 cells, and by assessing antibacterial activity via growth assays and antibiotic diffusion assays in agar plates inoculated with Gram-positive and Gram-negative bacteria. Results showed that fendiline has VGSC blocking and antiproliferative effects in GH3 cells, has antibacterial activity against Gram-positive bacteria, and has no intrinsic antiviral-inducing activity in cells. Fendiline was toxic at doses > 30 M and inhibits lipopolysaccharide (LPS)-induced nitric oxide production at higher concentrations due to its toxic effects on the macrophage cells. However, fendiline did not inhibit LPS-induced TNF production in the macrophage cells. Thus, fendiline has potent local anesthetic-like activity, antiproliferative, and antibacterial effects. The results here increased our understanding of fendiline and its mechanism of action.