Suppressing leukocyte Kv1.3-channels by commonly used drugs: A novel therapeutic target for schizophrenia?

Abstract

Recent studies revealed the involvement of "chronic inflammation" in the pathogenesis of schizophrenia. In schizophrenia and some neurodegenerative disorders that are caused by inflammation, T-lymphocytes and macrophages were hyperactivated or proliferated in the central nervous system, being accompanied by the overexpression of delayed rectifier K⁺-channels (Kv1.3) within the cells. In our previous basic studies, in addition to nonsteroidal anti-inflammatory drugs (NSAIDs) and statins, antibiotics (clarithromycin, chloroquine), anti-hypertensive drugs (nifedipine, benidipine, diltiazem, verapamil) and anti-allergic drugs (cetirizine, fexofenadine, azelastine, terfenadine) strongly suppressed the Kv1.3-channel activity and pro-inflammatory cytokine production from lymphocytes. Given such pharmacological properties of these commonly used drugs, they may be useful in the treatment of schizophrenia, in which the enhanced cellular immunity and the subsequent release of excessive cytokines are responsible for the pathogenesis.