Document Report Card

ID: ALA1128589

Journal: J Med Chem

Title: Novel benzo[b]quinolizinium cations as uncompetitive N-methyl-D-aspartic acid (NMDA) antagonists: the relationship between log D and agonist independent (closed) NMDA channel block.

Authors: Earley WG, Kumar V, Mallamo JP, Subramanyam C, Dority JA, Miller MS, DeHaven-Hudkins DL, Aimone LD, Kelly MD, Ault B.

Abstract: A series of permanently charged benzo[b]quinolizinium cations having lower lipophilicity than MK-801 or phencyclidine (PCP) were synthesized. Data relating agonist independent block of N-methyl-D-aspartic acid (NMDA) ion channels to log D are described. Closed channel access is predicted to result in a more noncompetitive profile of antagonism compared to selective open channel blockers, which are uncompetitive inhibitors. Reduced closed channel block may underlie the absence of PCP or MK-801-like behavioral side effects observed for benzo[b]-quinolizinium cations.

CiteXplore: 7658445

DOI: 10.1021/jm00018a018