Journal article

Sodium channel blocking activity of AM-36 and sipatrigine (BW619C89): in vitro and in vivo evidence

JK Callaway, M Castillo-Melendez, SF Giardina, EK Krstew, PM Beart, B Jarrott

NEUROPHARMACOLOGY | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2004

Abstract

Sodium channel blockers are neuroprotective against cerebral ischemia in animal models. A novel neuroprotective compound AM-36, when screened for activity at the most common receptor and ion channel binding sites, revealed activity at site 2 Na+ channels. Studies then investigated this Na+ channel blocking activity in vitro and in vivo relative to other Na+ channel blockers, including the neuroprotective agent sipatrigine (BW619C89). AM-36 inhibited batrachotoxinin (BTX)-sensitive Na+ channel binding in rat brain homogenates with an IC50 of 0.28 microM. Veratridine (100 microM)-induced neurotoxicity in murine cerebellar granule cells was completely inhibited by AM-36 (1.7 microM) compared to..

View full abstract