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

A series of permanently charged benzo[b]quinolizinium cations having l ower 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 com pared to selective open channel blockers, which are uncompetitive inhi bitors. Reduced closed channel block may underlie the absence of PCP o r MK-801-like behavioral side effects observed for benzo[b]quinolizini um cations.