title: NGP1-01, a lipophilic polycyclic cage amine, is neuroprotective in focal ischemia.
abstract: NGP1-01, a member of the pentacycloundecylamine cage compound family, was recently shown to exhibit both NMDA receptor channel blocking and L-type calcium channel antagonism activity. In the present study, focal ischemia was induced in mice by permanent middle cerebral artery occlusion (MCAO) to test for potential neuroprotective properties of the compound. In female CD-1 mice injected 30 min before MCAO, NGP1-01 (20 mg/kg) reduced infarct area by 42.6% (P < 0.05) compared to vehicle-treated controls as visualized by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Concomitantly, NGP1-01 reduced brain swelling by 78.3% (P < 0.001), compared to vehicle (DMSO) treated controls. These data identify NGP1-01 and related compounds as potential lead structures to develop neuroprotective compounds based on a dual mechanism of action.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University HSC, Amarillo, 79106-1712, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mdzinarishvili
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Geldenhuys
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Abbruscato
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bickel
authors.forename: Jochen
authors.initials: J
authors.lastname: Klein
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Van der Schyf
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007511:Ischemia / Q000517:prevention & control*; D051379:Mice; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D013778:Tetrazolium Salts
chemical_list: D001952:Bridged-Ring Compounds; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; C049649:NGP 1-01; C009591:triphenyltetrazolium